Signal Transduction

Signal transduction is a mechanism that converts a stimulus to a cell into a specific cellular response, through which the cell makes modifications in either activity of enzymes or gene transcription. Signal transduction processes are often initiated through receptor ligation or stresses, and may involve a cascade of signals within the cell. With each step of the cascade, the signal can be amplified and eventually creates a change to the cell to achieve the desired cell response. Transmembrane receptors span the cell membrane, with part of the receptor outside and part inside the cell. The chemical signal binds to the outer portion of the receptor, changing its shape and conveying another signal inside the cell. The cascading series of intracellular biochemical events often involve phosphorylation cascade. Activated kinases can catalyze the transfer of a phosphate group to serine, threonine, or tyrosine residues on target proteins and regulate protein activity, localization, and protein-protein interactions. Activities modified by phosphorylation can in turn be terminated by the phosphatases.

 

Featured Proteins Related to Signal Transduction
BLNK Protein CD21 Protein Insulin Receptor Protein S100A6 Protein
BTLA Protein DLL4 Protein MAP3K8 Protein S100P Protein
CD44 Protein FGFR2 Protein p38 Protein HAI-2/SPINT2 Protein
CEACAM3 Protein GABARAP Protein NKp44/NCR2 Protein UCHL1 Protein
Chk1 Protein IL-32 Protein NOTCH1 Protein

 

Featured Antibodies Related to Signal Transduction
BLNK Antibody FLT3 Antibody HIF1AN Antibody PIK3R1 Antibody
C2 Antibody GABARAPL2 Antibody HtrA2/Omi Antibody PPM1G Antibody
CCR2 Antibody GPR37 Antibody KIR2DL4 Antibody RNF43 Antibody
CD300A Antibody GSK3B Antibody IkB alpha Antibody S100A4 Antibody
Placental Lactogen/CSH1 Antibody

Adaptor proteins are cell signaling molecules linking intracellular proteins, including cell surface receptors to cytosolic effectors. They play key roles in cellular signaling such as phosphorylation, dephosphorylation, signal transduction, organization of the cytoskeleton, cell adhesion, regulation of gene expression, all distinct yet interacting systems. In their pure form, adaptor proteins are devoid of any intrinsic enzymatic activity and serve as intracellular platforms for the amplification and coordinated assembly of multimeric protein complexes. A common feature of adaptor proteins is the organization in modular structures; a limited number of highly evolutionary conserved protein sequences (“domains” or “modules”) are combined to produce a diverse array of protein structures with specific cellular functions and diverse connecting capabilities.

Adaptor Proteins
APBA2  Kindlin-2  PDHX  STUB1 
APBB1IP/RIAM  FRS2  PHF11  SWAP70 
BAP31/BCAP31  GAB2  PXN  TANK 
BLNK  GAPDH  14-3-3 sigma  TICAM2 
CALD1/caldesmon  GRB2  SH2B1  TRADD 
CBL  SAM68  SAP/SH2D1A  TRAF1 
CD2AP  KPNA1/SRP1  SH2D2A  Sts1 
CIDEA  KPNA2  SHC1/SHCA  14-3-3 beta 
CIDE C  KPNA4  SOCS5  14-3-3 epsilon
RAIDD  LAT  SOCS6  14-3-3 gamma/YWHAG 
CRKL  LAT2/NTAL  SQSTM1  14-3-3 eta/YWHAH 
DAB2  MYD88  STAP1  14‑3‑3/YWHAQ 
DFFA/DFF45  NOD1  STIP1  YWHAZ
FADD 

The phosphatidylinositol 3′ –kinase (PI3K)-Akt signaling pathway is an intracellular signaling pathway important in regulating the cell cycle and is activated by many types of cellular stimuli or toxic insults. It regulates fundamental cellular functions such as transcription, translation, proliferation, growth, and survival in response to extracellular signals. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates.

Adaptor Proteins in the Akt Pathway
CD2AP  SAM68  14-3-3 sigma  TRADD 
CIDEA  LAT  SH2B1  14-3-3 beta 
CRKL  LAT2/NTAL  SAP/SH2D1A  14-3-3 epsilon 
FADD  MYD88  SHC1/SHCA  14-3-3 gamma/YWHAG 
FRS2  NOD1  SOCS5  14-3-3 eta/YWHAH 
GAB2  PHF11  SOCS6  14‑3‑3/YWHAQ 
GAPDH  PXN  SWAP70  YWHAZ
GRB2 
Intracellular Kinases in the Akt Pathway
AKT1  PKR  JNK2  PKC epsilon/PRKCE 
AKT2  FES  MST1/MSP/HGFL  PRKCG/PKCG 
AKT3  FYN  PAK2  PKC iota 
Aurora A  GRK5  PAK3  GLRX3/PRKCT 
BMX  IKK beta  PAK4  PRKCZ / PKC zeta 
B Raf  IKBKE/IKK-i  PDPK1  Protein Kinase D2/PRKD2 
BTK  Integrin Linked Kinase/ILK  PI3 Kinase p110 beta/PIK3CB  PKC nu 
CAMKI  IRAK4  PIK3R1  PTK2/FAK1 
CaMKII alpha/CAMK2A  JAK1  PIK3R2  Brk 
CaMKII beta/CAMK2B  Lyn  PIK3R4  RAF1 
CaMKII/CAMK2G  MEK1  PIM1  RIPK1/RIP1 
CAMKK1  MEK2  PINK1  RIP3/RIPK3 
CDK1  MEK3/MKK3  PRK2/Prkcl2  RORC 
CDK2  MKK4  PLK1  RSK2 
CDK4  MEK5/MAP2K5  PLK3  MSK1 
Chk1  MKK6  AMPK alpha 1/PRKAA1  S6K1/RPS6KB1 
CHEK2  MLK3  AMPK  RPS6KB2 
CROT  MAP3K3/MEKK3  PRKAB1  SGK1/SGK 
Casein Kinase 1 alpha  MAP3K7/TAK1  PRKAB2  Sphingosine Kinase 1 
Casein Kinase 1 delta  ERK2  PRKACA  Src 
CSNK1E  MAPK10/JNK3  PRKACB  SRPK2 
CSNK1G1  MAPK11  PRKAR1B  LKB1 
CK2 alpha/CSNK2A1  p38  PKC alpha/PRKCA  MST2/STK3 
Casein Kinase 2 beta  ERK1/MAPK3  PRKCB  YES1 
ZIP Kinase/DAPK3  ERK5/BMK1/MAPK7  PKC delta/PRKCD  ZAP70
DGKZ  JNK1 
Phosphatases in the Akt Pathway
Acid Phosphatase/ACP1  FKBP12  Calcineurin B/PPP3R1  SHP2 
Calmodulin 1/CALM1  FKBP5/FKBP51  PTEN  TCPTP 
CDC25A  PPIG  PTP4A2  SHP-1 
DUSP1  PPP1CA  PTP4A3  CD45 
DUSP6  PPP1R1B  PTP1B  DEP-1
Laforin/EPM2A  Calcineurin A/PPP3CA 
Phospholipases, Small GTPases, and Other Molecules in the Akt Pathway
AKT1S1/PRAS40  LAX1 RAB25  RPTOR 
APP/Protease nexin-II  MAPKAP1  RAB27A  RRAS2 
beta Arrestin 1/ARRB1  PALLD  Rack1  SPRY1 
Beta Arrestin 2/ARRB2  RKIP/PEBP1  RALA  SPRY2 
Caveolin-1  PLA2G2A  RAP1A  STIM1 
p21/WAF1/CDKN1A  PLA2G4A  RAP1B  TOB1 
JAB1/CSN5  PLD1  RASSF2  Vinculin 
GSTA4  PRR5  RHEB  WASF1
Hsp27/HSPB1 
Receptor Tyrosine Kinases (RTKs) in the Akt Pathway
c-Abl/ABL1  ErbB4  c-Kit  PPP2CB 
AXL  FGF1  Mer  RET 
CSF1R  FLT1  RON/CD136  ROR1 
DDR1  VEGFR3/FLT4  TrkA  ROR2 
EphA1  IGF1R  TrkB  RYK 
Her2/ERBB2  Insulin Receptor  TrkC  STYK1/NOK 
HER3/ERBB3  VEGFR2/KDR  PDGFRA  TIE2
Transcription Factors in the Akt Pathway
ADNP  HMGB1  NANOG  SLUG 
Aryl Hydrocarbon Receptor  HSF1  Neurogenin-3  SOX5 
ARNT/HIF1 beta  IRF3/IRF-3  NFAT2/NFATC1  STAT1 
MASH1/ASCL1  c-Jun  NKX2.5  STAT3 
ATF2  KLF5  NR4A2 TAL1 
ATF-4  LEF1  NRF1  TGIF1 
DLX5  MAX  Nonstructural protein 1/NS1  p53 
EGR1  MEF2C Olig2  p63 
ELK1  MITF  PAX3  TRPS1 
HIF-2-alpha  MXI1  PAX6  WT1 
c-Fos  MYB  REL  ZBTB16/PLZF 
FOXM1  c-Myc/MYC  NF-kB p65  ZBTB17 
GATA2  Myogenin  SETD2  Rex-1/ZFP42
GATA3 
Translation Regulation by the Akt Pathway
EEF2K  4EBP1  IRAK4  PDCD4 
EIF4B  eIF5A  LIN28A  RPS6
Ubiquitin-related Molecules in the Akt Pathway
cIAP1  SKP2  MuRF1/TRIM63  Ubc13/UBE2N 
BRCA1  SMURF2  Ubiquitin Activating Enzyme E1/UBA1  UBE2V1 
CBL  STUB1  UBE2C  UCHL1 
MDM2  A20/TNFAIP3  UBE2F  UCHL3 
NEDD4  TRAF1  UbcH7/UBE2L3  UBPY/USP8

Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Despite its simplicity, recent progress has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles, which are sometimes complex. Autophagy consists of several sequential steps–sequestration, transport to lysosomes, degradation, and utilization of degradation products–and each step may exert different function. In this review, the process of autophagy is summarized, and the role of autophagy is discussed in a process-based manner.

AMPK (AMP-activated Protein Kinases)
AMPK alpha 1/PRKAA1  PRKAB1  PRKAG1  PRKAG3
AMPK  PRKAB2 
ATG Family
ATG10/Apg10  ATG4B  Beclin 1/BECN1  GABARAPL2 
ATG12  ATG5/APG5L  GABARAP  MAP1LC3A 
Apg3/ATG3  Apg7/ATG7  GABARAPL1  LC3B
ATG4A 
mTOR Complexes
AKT1S1/PRAS40  MAPKAP1  MTOR  RICTOR 
DEPTOR  MLST8  PRR5  RPTOR
Other Autophagy-related Proteins
Bcl-2  p27/Kip1/CDKN1B  SIRT1  TFEB 
Bcl-XL  CUG-BP1/CELF1  SIRT2  TMEM59 
BNIP3  CHMP2B  Acid sphingomyelinase/SMPD1  UVRAG 
BNIP3L  PFKFB3  SQSTM1  VCP
C9orf72 
Rab Proteins
RAB25  RAB27A  RAB7A

Calcium-binding proteins have a vital role in calcium homeostasis by buffering and probably also have a neuroprotective function. Fluctuations in intracellular calcium (Ca2+) are central to orderly neurotransmission and the operation of a wide range of cellular functions. In the lateral BST, a few calbindin D-28k-immunoreactive neurons were scattered in a moderately stained neuropil. Staining of calretinin, another calcium-binding protein, was intense in the rostral pole of the lateral BST, continuous with the caudal ventral striatum. Small calretinin-immunoreactive cell bodies were observed in the lateral BST, but their dendrites could not be clearly visualized because of the intensity of background staining

Calcium-binding Proteins and Related Molecules
Iba1  CAMKK1  PDP1/PDP  S100A4 
Calbindin  CAMKK2  Calcineurin A/PPP3CA  S100A6 
CALB2  CIB1  Calcineurin B/PPP3R1  Psoriasin/S100A7 
Calcitonin receptor  CLSTN1  PRKD1  S100A8 
CALD1/caldesmon  CLSTN2  Parvalbumin/PVALB  S100A9 
Calmodulin 1/CALM1  CLSTN3  S100A1  S100B 
Calreticulin  DCLK1  S100A10  S100P 
Calreticulin 3/CALR3  DOC2A  S100A11  SMOC1 
CAMKI  GPRC6A  S100A12  SMOC2 
CaMKII alpha/CAMK2A  HAX1  S100A13  Synaptotagmin 1/SYT1 
CaMKII beta/CAMK2B  NUCB2/Nucleobindin 2  S100A16  TCTP/TPT1 
CaMKII/CAMK2G  PCDH12/Protocadherin 12  S100A2  WFS1

Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease. A variety of stressors, including strong mitogenic signals, DNA damage, and non-genotoxic chromatin perturbations cause cellular senescence – a state of permanent cell cycle arrest. Cellular senescence, although useful in young organisms to prevent cancer, is thought to promote aging. The most consistent determinant of life-span in eukaryotes is the mitogenic growth hormone/IGF-I pathway. However, premature aging syndromes caused by defects in the cellular response/repair to DNA damage indicate the role of accumulated damage. The complex biology of aging is impacted by both environmental and genetic factors: stochastic DNA damage causes decline of function, and genetics determines the rates of damage accumulation and functional decline.

DNA Damage and Repair
BABAM1/HSPC142  CDKN2B/p15 INK4b  c-Myc/MYC  p53 
Bcl-2  Chk1  DNA-PKcs/PRKDC  UBE2F 
BRCA1  CHEK2  PSME3  Ubc13/UBE2N 
Catalase  ERCC1  RbAp48  UBE2T 
CDC25A  FANCA  SOD1  UBE2V1 
CDC25C  FTO  DcR2/TRAIL R4  UBE2V2 
CDC42  MEN1  TOPBP1  XPA
p21/WAF1/CDKN1A  MSH2 
Growth Hormone/IGF-I Axis
AKT1  Insulin Receptor  PRKAB1  SGK1/SGK 
Placental Lactogen/CSH1  Klotho beta  PRKAB2  SIRT1 
Insulin-degrading enzyme  PCSK1  Prolactin  SIRT2 
Insulin  PCSK2  Prolactin Receptor  SIRT3 
INSL3  PDPK1  PTEN  SIRT5 
INSL4  AMPK alpha 1/PRKAA1  RORC  SPRED1
INSL6  AMPK 
ROS and Stress Resistance
RAGE  MEK1  ERK5/BMK1/MAPK7  RAF1 
Bcl-2  MEK2  p67phox  RORC 
B Raf  MEK5/MAP2K5  NOX4  SETD2 
BUB3  ERK2  PRKACA  SOD1 
GPX1  ERK1/MAPK3  PRKACB  SOD2/Mn-SOD 
GPX2  MAPK6  PRKAR1B  SOD3
HIF1AN 

In humans, circadian rhythms influence the sleep-wake cycle. They also affect other physiological processes such as nervous system activity, hormone production, blood pressure, appetite, digestion and body temperature. Even our mood and cognitive ability is influenced by it. Clock is a basic helix-loop-helix-PAS transcription factor that heterodimerizes with BMAL1. Together these transcription factors bind to E box elements (CACGTG) within the promoter of Period circadian genes (PER1 and PER2) stimulating their transcription. CRY1 is a critical component of the circadian oscillator that represses CLOCK-BMAL1 mediated transcription when translocated into the nucleus. PER1, also known as RIGUI, influences circadian rhythms by interacting with, and stabilizing, other circadian regulatory proteins.

Circadian Rhythm Molecules
KAT13D/CLOCK  HTR7  MT2A

G protein-coupled receptors (GPCRs),G-protein linked receptors, serpentine receptors, or heptahelical receptors are the largest superfamily of membrane proteins in the human genome and they are integral membrane proteins with seven membrane-spanning helices. Upon binding to a ligand – which can range from small molecules like cyclic AMP to peptides and large proteins – GPCRs undergo a conformational change that activates heterotrimeric G proteins (guanine nucleotide-binding proteins), which are important for transmitting the extracellular, ligand signal to the cell interior. G-Proteins can be classified by homologous structure and via common ligand subtypes.

Bioactive Lipid G Protein-Coupled Receptors
GPCR GPR40/FFAR1  LTB4R  S1PR1  S1PR2
GPR34  PTAFR 
Chemokine Receptors
ACKR2  CCR5  IL8Ra/CXCR1/CD181  CXCR5 
CCR1  CCR7/CD197  IL8Rb/CXCR2/CD182  CXCR6 
CCR2  CCR8  CXCR3  GPR75
CCR3  CCR9  CXCR4/CD184 
Frizzled Receptors
FZD1  Frizzled 2  Frizzled 5  Frizzled-9/FZD9
Frizzled 10  Frizzled 4  Frizzled 6 
Neurotransmitter G Protein-Coupled Receptors
PACAP receptor/ADCYAP1R1  Dopamine D2 Receptor/DRD2 GRM2  HTR7 
ADRA2B  GPR35  GRM4  MRGPRF 
ADRB2  GPR45  HCRTR2 / OX2R  MT2A 
AGTR1/AT1  GPR61  5HT2B/HTR2B  NMUR2 
AGTR-2  GRIK2  HTR4/5-HT4  OPRL1/nociceptin receptor
CD44 
Orphan G Protein-Coupled Receptors
GPR20  GPR37L1  GPR83  GPR85
GPR37  GPR6 
Other G Protein-Coupled Receptors
Thrombin Receptor  GPBAR1  GPR35  P2RY6
PAR2 
Peptide Hormone G Protein-Coupled Receptors
PACAP receptor/ADCYAP1R1  BDKRB1  HCRTR2 / OX2R  RXFP2 
AGTR1/AT1  CD44  PTH1R  RXFP3 
AGTR-2  GLP1R  RAMP1  SSTR2
APJ Receptor/APLNR  GRPR 

Protein kinases transfer phosphate groups from ATP to serine, threonine, or tyrosine residues on protein peptide substrates, directly affecting the activity and function of the target. Radiolabel studies suggest that approximately 30% of proteins in eukaryotic cells are subject to phosphorylation. Kinase activity, a crucial post-translational modification, regulates a broad range of cellular activities including the cell cycle, differentiation, metabolism, and neuronal communication. In addition, abnormal activity of Akt, ERK, JNK, PKC, PKA, p38, and other MAPK are implicated in many disease states. R&D Systems offers a range of quality products for the detection of protein phosphorylation, which include kinase activity assays, phospho-specific antibodies, ELISA, and more.

Akt Isoforms
AKT1  AKT2  AKT3
AMPK (AMP-activated Protein Kinases)
AMPK alpha 1/PRKAA1  PRKAB1  PRKAG1  PRKAG3
AMPK  PRKAB2 
CaM Kinases
CAMKI  CaMKII beta/CAMK2B  CaMKII/CAMK2G  CAMKK1
CaMKII alpha/CAMK2A 
Carbohydrate Kinases
ADK  Glucokinase  HK2  PFKFB3 
FAM20B  GNE/GLCNE  Ketohexokinase/KHK  Xylulokinase/XYLB
FN3K  Hexokinase 1/HK1  NAGK 
Casein Kinases
Casein Kinase 1 alpha  CSNK1E  CK2 alpha/CSNK2A1  Casein Kinase 2 beta
Casein Kinase 1 delta  CSNK1G1 
Creatin Kinase
Creatine kinase B  CKM
Cyclin-Dependent Protein Kinases (CDKs)
CDK1  CDK4  Cdk5  CDK8
CDK2 
DGK Family
DGKA  DGKD  DGKG  DGKQ 
DGKB  DGKE  DGKI  DGKZ
DYRKs (Dual-specificity Tyrosine-[Y]-phosphorylation Regulated Kinases)
DYRK1A  DYRK2  DYRK3
ERK (Extracellular Signal-regulated Kinases)
ERK2  ERK1/MAPK3  MAPK4  ERK5/BMK1/MAPK7
P38 Gamma/MAPK12 
GRKs (G Protein-coupled Receptor Kinases)
GRK1  ADRBK2  GRK5  GRK7
IkB Kinase (IKK)
CHUK  IKK beta  IKBKE/IKK-i
IRAK Family
IRAK2  IRAK4
Jak Kinases
JAK1  JAK2  JAK3  TYK2
JNK
MAPK10/JNK3  JNK1  JNK2
MAP3K
ARAF  MAP3K14  MAP3K3/MEKK3  MAP3K8 
B Raf  MAP3K2/MEKK2  MAP3K5/ASK1  RAF1 
MAP3K10/MLK2  MLK4  MAP3K7/TAK1  TAOK2
MLK3 
Mitogen-Activated Protein Kinase Kinases (MEKs/MKKs)
MEK1  MEK3/MKK3 MEK5/MAP2K5  MKK6
MEK2  MKK4 
MSK
MSK1
p38 MAP Kinases
MAPK11  P38 Gamma/MAPK12  P38 Delta/MAPK13  p38
PAK (p21-activated Kinases)
PAK1  PAK3  PAK7  PAK6
PAK2  PAK4 
PI 3-Kinases (Phosphoinositide 3-Kinases)
PIK3C2B  PI3 Kinase p110 beta/PIK3CB  PIK3R1  PIK3R4 
PIK3C3  PIK3CD  PIK3R2  PIK3R5
PKA Isoforms
PRKACA  PRKACB  PRKAR1B
PKC Isoforms
PRK2/Prkcl2  PKC delta/PRKCD  PRKCG/PKCG  GLRX3/PRKCT 
PKC alpha/PRKCA  PKC epsilon/PRKCE  PKC iota  PRKCZ / PKC zeta
PRKCB 
Polo-like Kinases
PLK1  PLK3
Ribosomal Protein S6 Kinases (RSK)
RSK1/RPS6KA1  RSK3  RSK2  RSK4
Src Kinases
BLK  FYN  Lyn  Src 
FGR  HCK  SHB  YES1
FRK 

ITIMs (immunoreceptor tyrosine-based inhibition motif; S/I/V/LxYxxI/V/L) and ITAMs (immunoreceptor tyrosine-based activation motif; consensus sequence YxxI/Lx6-12YxxI/L) are phosphorylation motifs found in a large number of receptors or adaptor proteins. Phosphorylated ITAMs serve as docking sites for tandem SH2 domains of Syk family kinases, whereas phosphorylated ITIMs recruit tyrosine phosphatases. Signaling through ITAM-bearing receptors usually results in cell activation, while engagement of ITIM-bearing receptors is usually inhibitory, although exceptions have been described. The majority of these receptors are involved in tumor development and regulation of the immune system, although some also function in tissues such as bone and brain.

ITIM/ITAM Immunoreceptors and Related Molecules
BTLA  CLEC-1  KIR2DL3  NKp44/NCR2 
CD22  CLEC-2  KIR2DL4  NKp30/NCR3 
CD226  CLEC4A  KIR2DL5  PD-1 
2B4/CD244  CLEC5A  KIR3DL1  PDCD6 
CD28  Dectin-1  KIR3DL3  CD31 
CD300A  CTLA-4  KIR3DS1  PILRA 
CD300C  CD89  NKp80/KLRF1  SHP2 
CD300E  CD23  KLRG1  SHP-1 
CD300LB  CD32A  LAIR1  SIGLEC10 
CD300f/CD300LF  CD32B/Fcgr2b  LAIR2  SIGLEC5 
CD33  CD16a  LILRA3 SIGLEC6 
CD3 epsilon/CD3e  CD16b  LILRA4/CD85g  SIRPB1 
CD3G  FCRL1  LILRA5  SLAM/CD150 
CD5  FCRL3  LILRB1  SLAMF6 
CD6  IRTA1/FCRL4  ILT4  SLAMF7/CD319 
CD72  FCRL6  LILRB3  SLAMF8 
CD84  ITGA2B/CD41  CD229  TIGIT 
CEACAM1  Integrin beta 3  MS4A2  TLT-1/TREML1 
CEACAM3  KIR2DL1  NKp46/NCR1  TREML2
CLEC12A 

The JAK/STAT pathway is a principal signaling mechanism for many cytokines and growth factors and provides a direct mechanism to translate extracellular signals into transcriptional responses. Activation of this pathway stimulates cell proliferation, differentiation, migration, growth, survival, apoptosis, and pathogen resistance. These cellular events are critical to hematopoiesis, immune development, growth, adipogenesis, mammary gland development and lactation, and other processes. Mutations that affect JAK/STAT pathway activity are important in inflammatory disease and hematological malignancies, including erythrocytosis and an array of leukemias. JAK inhibitors are also being tested for use in multiple myeloma. Additionally, the JAK/STAT pathway mediates the effects of drug treatments of anemia, thrombocytopenia, and neutropenia, as well as antiviral and antiproliferative agents.

Jak Kinases
JAK1  JAK2  JAK3  TYK2
Negative Regulators of the Jak/STAT Pathway
AGTR1/AT1  Growth Hormone  IL5RA  C-MPL 
BLK  IFNGR1  IL-6R  TrkB 
BRCA1  IL28A  gp130/IL6ST  OSMR 
CaMKII beta/CAMK2B  IGF1R  IL7R alpha/CD127  PDGFRA 
CaMKII/CAMK2G  IKBKE/IKK-i  IL9R PPP2CB 
CCR1  IL10RA  Insulin Receptor  PKC delta/PRKCD 
CCR2  IL10RB  JAK1  Prolactin Receptor 
CCR5  IL11RA  c-Jun  PTAFR 
CNTFR  IL12RB1  VEGFR2/KDR  RORC 
CSF1R  IL12RB2  c-Kit  SH2B1 
CSF3R/G-CSFR  IL-15  Leptin Receptor  Src 
CXCR4/CD184  IL15RA  LIFR  STAT1 
Her2/ERBB2  IL20RB  Lyn  STAT2 
ErbB4  IL21  ERK2  STAT3 
Thrombin Receptor  IL21 Receptor  MAPK11  STAT4 
FGF1  IL23 Receptor  p38  STAT6 
FLT1  CD25/IL2RA  ERK1/MAPK3  STIP1 
VEGFR3/FLT4  CD122/IL2RB  JNK1  TIE2 
c-Fos  IL-32  Mer  YES1
FYN  IL4R 
Positive Regulators of the Jak/STAT Pathway
BRCA1  IKBKE/IKK-i  p38  RORC 
CaMKII beta/CAMK2B  c-Jun  ERK1/MAPK3  SH2B1 
CaMKII/CAMK2G  ERK2  JNK1  STIP1
c-Fos  MAPK11  PKC delta/PRKCD 
Receptors in the Jak/STAT Pathway
AGTR1/AT1  VEGFR3/FLT4  IL21  VEGFR2/KDR 
CCR1  Growth Hormone  IL21 Receptor  c-Kit 
CCR2  IFNGR1  IL23 Receptor  Leptin Receptor 
CCR5  IL28A  CD25/IL2RA  LIFR 
CNTFR  IGF1R  CD122/IL2RB  Mer 
CSF1R  IL10RA  IL-32  C-MPL 
CSF3R/G-CSFR  IL10RB  IL4R  TrkB 
CXCR4/CD184  IL11RA  IL5RA  OSMR 
Her2/ERBB2  IL12RB1  IL-6R  PDGFRA 
ErbB4  IL12RB2  gp130/IL6ST  PPP2CB 
Thrombin Receptor  IL-15  IL7R alpha/CD127  Prolactin Receptor 
FGF1  IL15RA  IL9R  PTAFR 
FLT1  IL20RB  Insulin Receptor  TIE2
Src Kinases
BLK  FYN  Lyn  Src 
FGR  HCK  SHB  YES1
FRK 
STAT
STAT1  STAT3  STAT4  STAT6
STAT2 

Neurotransmitter receptors are expressed on the surface of post-synaptic cells to bind ligand-specific neurotransmitters and hormones. They are also expressed on presynaptic cells to provide feedback mechanisms and attenuate excessive neurotransmitter release. The majority of neurotransmitter receptors are integral membrane proteins with seven transmembrane domains, commonly coupled to G-proteins. Binding of a ligand to its specific neurotransmitter receptor may result in the activation of a myriad of cell signal transduction pathways and modulation of ion channel homeostasis.

Calcium-binding Proteins and Related Molecules
Iba1  CAMKK1  PDP1/PDP  S100A4 
Calbindin  CAMKK2  Calcineurin A/PPP3CA  S100A6 
CALB2  CIB1  Calcineurin B/PPP3R1  Psoriasin/S100A7 
Calcitonin receptor  CLSTN1  PRKD1  S100A8 
CALD1/caldesmon  CLSTN2  Parvalbumin/PVALB  S100A9 
Calmodulin 1/CALM1  CLSTN3  S100A1  S100B 
Calreticulin  DCLK1  S100A10  S100P 
Calreticulin 3/CALR3  DOC2A  S100A11  SMOC1 
CAMKI  GPRC6A  S100A12  SMOC2 
CaMKII alpha/CAMK2A  HAX1  S100A13  Synaptotagmin 1/SYT1 
CaMKII beta/CAMK2B  NUCB2/Nucleobindin 2  S100A16  TCTP/TPT1 
CaMKII/CAMK2G  PCDH12/Protocadherin 12  S100A2  WFS1
GABA Receptors
GABARAP  GABRA4  GABA Receptor Epsilon  GABRR1 
GABARAPL1  GABRA5  GABRG1  GABRR2 
GABARAPL2  GABRA6  GABRG2  GABRR3 
GABBR1  GABRB1  GABRG3  GAD67 
GABRA1  GABRB2  GABRP/GABA A receptor pi  GAD65 
GABRA2  GABRB3  GABRQ  Gephyrin/GPHN
GABRA3  GABRD 
Glutamate Receptors
GRIK2  GRM4  HOMER1  HOMER2
GRM2 
Ion Channels and Regulators
HCN4  P2RX1  P2RX5  SLC12A5 
KCNB2  P2RX2  P2RX6  SLC12A6 
KCNC1  P2RX3  P2RX7  SLC8A1 
KCNK15  P2RX4  SLC12A4  TRPM8
ORAI1 
Neurotransmitter G Protein-Coupled Receptors
PACAP receptor/ADCYAP1R1  Dopamine D2 Receptor/DRD2  GRM2  HTR7 
ADRA2B  GPR35  GRM4  MRGPRF 
ADRB2  GPR45  HCRTR2 / OX2R  MT2A 
AGTR1/AT1  GPR61  5HT2B/HTR2B  NMUR2 
AGTR-2  GRIK2  HTR4/5-HT4  OPRL1/nociceptin receptor
CD44 
Neurotransmitter Transporters
DPP10  PANX1/Pannexin 1  EAAT1/SLC1A3  SLC6A1 
DPP6  PANX3/Pannexin 3  SLC22A1  SLC6A7
NUP85 

Nuclear factor kappa beta (NFkB) is a nearly ubiquitous pathway responsible for mediating DNA transcription, and therefore cell function. The pathway is activated by a variety of stimuli including cellular stress, cytokines, free radicals, UV radiation, oxidized LDL, and bacterial/viral infection. Activated NFkB is translocated to the nucleus where it binds to specific sequences of DNA called response elements. This DNA/NFkB complex then recruits RNA polymerase and other coactivators, which transcribe downstream DNA into mRNA, for protein synthesis.NFkB1 and NFkB2 are members of the Rel/NFkB family of transcription factors that also includes RelA, c-Rel, and RelB. Rel/NFkB members regulate the expression of genes that participate in immune, apoptotic and oncogenic processes. NFkB is predominantly localized in the cytoplasm as a complex with inhibitory IkB proteins and is released and translocated to the nucleus after phosphorylation of IkB. Both NFkB1 (105 kDa) and NFkB2 (100 kDa) are synthesized as precursor molecules that are proteolytically cleaved to 50 and 52 kDa active subunits. NFkB appears to have contradictory functions in apoptosis and cell survival. NFkB mediates the survival response of many signals by inhibiting p53-dependent apoptosis and up-regulating anti-apoptotic members of the Bcl-2 family, and caspase inhibitors such as XIAP, and FLIP. In contrast, NFkB is also activated by apoptotic stimuli involved in DNA damage and mediates upregulation of pro-apoptotic genes such as TRAIL R2/DR5, Fas, and Fas ligand.

IkB Kinase (IKK)
CHUK  IKK beta  IKBKE/IKK-i
IkB Proteins
IkB alpha  IKB beta/NFKBIB
NFkB
p100/p52  REL  NF-kB p65  RELB
Post-translational Modification of NFkB/IkB
BTRC  MAP3K3/MEKK3  SENP2  Ubiquitin/UBB 
COMMD1/MURR1  MAP3K7/TAK1  SHARPIN  UBD 
CYLD  NOD1  SUMO1  Ubc13/UBE2N 
FBXW7  OTULIN  SUMO2  UBE2V1 
MAP3K14  PIAS3  Sumo 3  UBE2V2
MAP3K2/MEKK2  SENP1  SUMO4 
Regulator of NFkB
BCR  MALT1  SECTM1  USP11 
CARD11  LYRIC  SQSTM1  USP4 
CD7  OTUD7B  TBK1  VCP 
EDA2R  RIPK1/RIP1  TMEM173  WLS 
Erbin  RIP3/RIPK3  A20/TNFAIP3  ZC3H12A 
HIF1AN  RNF31  TSPAN6  ZG16B
LRRC4 
Survivin / IAPs
cIAP1  Survivin  NAIP  XIAP
cIAP2/BIRC3  Livin/BIRC7 

The Notch signaling pathway is a highly conserved cell signaling system present in most multicellular organisms. Notch signaling plays a pivotal role in the regulation of many fundamental cellular processes such as proliferation, stem cell maintenance and differentiation during embryonic and adult development. The notch cascade consists of notch and notch ligands, as well as intracellular proteins transmitting the notch signal to the cell’s nucleus. In mammalian cells, there are four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4, which display both redundant and unique functions. Notch receptors are large single pass Type I transmembrane proteins. The extracellular domain of all Notch proteins contains 29–36 tandem epidermal growth factor (EGF)-like repeats, some of which mediate interactions with ligand. After specific ligand binding, the intracellular part of the Notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor RBP-J. In the absence of activated Notch, RBP-J represses Notch target genes by recruiting a corepressor complex. Notch signaling is dysregulated in many cancers, and faulty notch signaling is implicated in many diseases including CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy), T-ALL (T-cell acute lymphoblastic leukemia), Alagille syndrome, MS (Multiple Sclerosis), and myriad other disease states.

Notch Pathway
Alpha4GnT/A4GNT  DLL4  NOTCH1  RBPJ 
APH1A  DTX1  NOTCH2  RITA1 
Contactin-1  GSK3B  POFUT1  SIAH1 
Cytochrome b5/CYB5A  Jagged 1  PSEN1  SLC35C2 
DLL1  LFNG/Lunatic Fringe  PSENEN  TSPAN5

Protein phosphorylation is a reversible and dynamic post-translational modification that is governed by the opposing activities of protein phosphatases and kinases. Protein phosphatases remove phosphate groups covalently attached to serine, threonine, and tyrosine residues. By counteracting the activities of kinases, phosphatases play an important role in the control of a wide variety of cellular functions including cell cycle checkpoints, responsiveness to growth factors, contact inhibition, and cellular motility. Disturbances in phosphatase activity are implicated in a wide variety of disease states such as colon cancer, obesity, and immunodeficiencies. A number of successful drugs have been developed that target protein phosphatases.

Phosphatases and Regulators
Acetylcholinesterase  ENPP3  CD73  Ppp2r4 
Acid Phosphatase/ACP1  ENPP4  NUDT5  PTP1B 
ACP5  ENPP-5  PDP1/PDP  SHP2 
Prostatic Acid Phosphatase  ENPP6  LPPR4  PTPN13 
Alkaline phosphatase  ENPP7  PPA1  PTPN14 
Alkaline Phosphatase/ALPL  CD39  Cyclophilin A  TCPTP 
Alkaline Phosphatase/PLAP  Laforin/EPM2A  Cyclophilin B  SHP-1 
Butyrylcholinesterase  FBP1  PPM1A  PTPN9 
Calmodulin 1/CALM1  FKBP12  PPM1B  PTP alpha/PTPRA 
CANT1  FKBP1B  PPM1G  CD45 
CDC14A  FKBP2  PPM1L  PTPRD 
CDC25A  FKBP25/FKBP3  PPP1CA  PTPRG 
Cdc25B  FKBP52/FKBP4  PPP1R10  DEP-1 
CDC25C  FKBP8/FKBP38  PPP1R1B  PTPRM 
DUSP1  ILKAP  PPP1R9B  PTPRT 
DUSP3  IMPA1  PPP4C  PTPRU 
DUSP6  IMPAD1  PPP5C  PTPRZ1 
ELFN1  INPP5D  PTEN  SIRP gamma/SIRPG 
ELFN2  INPPL1  PTP4A1  TIGAR/C12orf5 
ENPP1  LPIN2  PTP4A2  Sts1 
ENPP2  LPIN3  PTP4A3  ZEB2

The first phosphoserine/threonine-binding molecules that were identified were members of a family of dimeric proteins called 14-3-3 that were first identified as abundant polypeptides of unknown function in brain; they were later identified as activators of tryptophan and tyrosine hydroxylase and as inhibitors or activators of PKCs. Mammalian cells contain 7 distinct 14-3-3 gene products (denoted β, γ, e, η, σ, t, and ζ), while plants and fungicontain between 2 and 15. Several of the mammalian 14-3-3 isotypes are subject to phosphorylation, although the role that phosphorylation plays in 14-3-3 function remains speculative.

phospho-Serine/phospho-Threonine Binding Proteins
IRS1  14-3-3 beta  14-3-3 gamma/YWHAG  14‑3‑3/YWHAQ 
IRS2  14-3-3 epsilon  14-3-3 eta/YWHAH  YWHAZ
14-3-3 sigma 

Receptor Tyrosine Kinases (RTKs) are widely expressed transmembrane proteins that act as receptors for growth factors, neurotrophic factors, and other extracellular signaling molecules. Upon ligand binding, they undergo tyrosine phosphorylation at specific residues in the cytoplasmic tail. This leads to the binding of protein substrates and/or the establishment docking sites for adaptor proteins involved in RTK-mediated signal transduction. RTKs have critical functions in several developmental processes including regulating cell survival, proliferation, and motility. When unregulated, they play prominent roles in cancer formation. The simplest receptor tyrosine kinases (RTKs) have three domains: a ligand binding domain outside the cell, a single membrane-spanning domain, and a tyrosine kinase domain inside the cell. The ligands are usually diffusible peptides or small proteins produced elsewhere in the organism, and are typically growth factors, cytokines and hormones. In the absence of a ligand the receptor is inactive.

Receptor Tyrosine Kinases (RTKs)
AXL  FGFR2  Insulin Receptor  TrkB 
CSF1R FGFR3  VEGFR2/KDR  TrkC 
DDR1  FGFR4  c-Kit  PDGFRA 
DDR2  FGFRL1  Mer  PDGFRB 
EGFR  FLT1  c-MET  RET 
Her2/ERBB2  FLT3  RON/CD136  STYK1/NOK 
HER3/ERBB3  VEGFR3/FLT4  MUSK  TIE2 
ErbB4  IGF1R  TrkA  Tie-1
FGFR1 

Members of the serine proteases are diverse with regard to their function, expression pattern and association with health and disease. Some are active in the coagulation cascade and the complement pathways while others are found specifically in the granules of cytotoxic T lymphocytes and natural killer cells (Granzymes) or in mast cells with trypsin-like specificity (Tryptases). Secreted tissue Kallikreins are cancer markers while transmembrane proteases such as Corin and Enterokinase are convertases. Their proteolytic activity is regulated by different Serpins and receptors such as uPAR and HAIs.

Serine Proteases and Regulators
alpha-2-macroglobulin  DPP10  Kallikrein 7/KLK7  PRSS3 
A2ML1  DPP4/CD26  Kallikrein 8  PRSS50 
Angiotensinogen  DPP6  KLK9  Prostasin/PRSS8 
Bikunin/AMBP  DPP2  Kallikrein 1B/KLKB1  PRTN3 
C1QA  DPP9  LRP1  Serpina3n 
C1QC  Neutrophil Elastase  MT2A  TBG 
CTRP3/C1QTNF3  Factor X  NPEPPS  SERPINA9 
CTRP4/C1QTNF4  Factor XI  OTOL1  SerpinB3 
C1QTNF5/CTRP5  Coagulation Factor II  PAMR1  SLPI 
CTRP9/C1QTNF9  Tissue Factor  PARL  SPINK1 
C1R  Factor VII  PCSK1  HAI-1 
C1RL  FAP  PCSK2  HAI-2/SPINT2 
C2  GranzymeA/GZMA  PCSK7  ST14 
Complement component 3  Granzyme B  PCSK9  TFPI 
CES1  HEBP1  RKIP/PEBP1  TFPI2 
CES3  HGF Activator/HGFA  Elafin  Thrombopoietin 
GM4738  Haptoglobin  tPA  TMPRSS11D 
CES7  Hepsin  uPAR/PLAUR  Enterokinase 
CFHR1  HTRA1  Prolyl Endopeptidase  TMPRSS5 
CFHR2  HtrA2/Omi  Protein C  TMPRSS9 
CFHR4  IGF1  EPCR  TPP1 
CFHR5  ITIH4  Protein S/PROS1  TPSAB1 
chymase 1  Kallikrein 1  Trypsin 1/PRSS1  TPSB2 
CORIN  Kallikrein 2/KLK2  PRSS2  TPSG1 
CD21  KLK4  PRSS21  HE4 
Chymotrypsin C  KLK5/Kallikrein 5  PRSS22  WFIKKN1 
Cathepsin A  Kallikrein 6  Marapsin  GASP-1/WFIKKN2

Degradation of a protein via the Ubiquitin Proteasome pathway involves two discrete and successive steps: tagging of the substrate protein by the covalent attachment of multiple Ubiquitin molecules (conjugation), and the subsequent degradation of the tagged protein by the 26S proteasome. Ubiquitin is conjugated to substrate proteins via an enzymatic cascade involving E1 (ubiquitin activating), E2 (ubiquitin conjugating) and E3 (ubiquitin ligating) enzymes. This classical function is associated with housekeeping roles, including the regulation of protein turnover, and antigenic-peptide generation. More recently, it has become evident that protein modification by Ubiquitin has non-degradative functions, including involvement in DNA repair and histone modification, vesicular trafficking pathways and endocytosis, and viral budding.

Although Ubiquitin is the most studied, there is a growing family of Ubiquitin-like proteins (UBLs) that modify cellular targets in a pathway that is parallel to but distinct from that of Ubiquitin. These alternative modifiers include: SUMO, NEDD8, ISG15, APG8, APG12, FAT10, UFM1, URM1, FUB1, and Hub1. Proteins conjugated to UBLs are typically not targeted for degradation by the proteasome, but rather function in diverse regulatory activities including transcription, DNA repair, signal transduction, and autophagy.

Deubiquitinating Enzymes (DUBs)
ATG4A  OTULIN  UCHL3  USP51 
ATG4B  SENP1  USP1  USP7 
CYLD  SENP2  USP14  UBPY/USP8 
OTUB1  SENP8  USP19  USP9X 
OTUB2  STAMBP  USP25  WDR48 
OTUD3  A20/TNFAIP3  USP28  YOD1 
OTUD7B  UCHL1  USP5  ZRANB1
E1 Ubiquitin/Ubl Activating Enzymes
Apg7/ATG7  SAE1  UBA3  UBA6
NAE1  Ubiquitin Activating Enzyme E1/UBA1  UBA5 
E2 Ubiquitin/Ubl Conjugating Enzymes
Apg3/ATG3  UBE2D4  UBC9/UBE2I  UBE2R2 
CDC34  UBCH6/UBE2E1  UBE2J2  UBE2S 
Rad6/UBE2A  UBE2E3  UBE2K  UBE2T 
UBE2B  UBE2F  UbcH7/UBE2L3  UBE2V1 
UBE2C  UBE2G1  Ube2L6  UBE2V2 
UBE2D1  UBE2G2  UBE2M  UBE2W 
UBE2D2  Ube2H  Ubc13/UBE2N  UFC1
UBE2D3 
E3 Ubiquitin Ligases
AMFR  MDM2  RNF43  TRAF5 
cIAP1  MIB1  RNF8  TRAF6 
cIAP2/BIRC3  MIB2  SART1  TRIM21 
BRCA1  NDFIP1  SKP2  KAP1/TRIM28 
BTRC  NEDD4  SMURF2  TRIM32 
CBL  GRAIL/RNF128  STUB1  TRIM5 
FBX15  RNF168  A20/TNFAIP3  MuRF1/TRIM63 
FBXW7  RING1B  TRAF1  UBE3A/E6AP 
ITCH  RNF31  TRAF2  ZNRF3
MARCH8  RNF4  TRAF3 
Proteasome
PSMA1  PSMB7  PSMB9  PSME2 
PSMA2  PSMB8  PSMD4  PSME3
PSMB10 
Ubiquitin
Ubiquitin/UBB
Ubiquitin-like Modifiers (UBLs) and Regulators
Fub1  PIAS2  SUMO2  UBC9/UBE2I 
GABARAP  PIAS3  Sumo 3  Ube2L6 
GABARAPL1  RANGAP1  SUMO4  UBE2M 
GABARAPL2  RNF4  KAP1/TRIM28  UFC1 
ISG15  SENP1  UBA5  UFM1 
MAP1LC3A  SENP2  UBD  URM1 
NEDD8  SENP8  UBE2F  ZMIZ1
NUB1  SUMO1 

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the name Wingless and the name Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

Three Wnt signaling pathways have been characterized: the canonical Wnt pathway, the noncanonical planar cell polarity pathway, and the noncanonical Wnt/calcium pathway. All three pathways are activated by the binding of a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the Dishevelled protein inside the cell. The canonical Wnt pathway leads to regulation of gene transcription, and is thought to be negatively regulated in part by the SPATS1 gene. The noncanonical planar cell polarity pathway regulates the cytoskeleton that is responsible for the shape of the cell. The noncanonical Wnt/calcium pathway regulates calcium inside the cell.

Wnt Inhibitors
DKK1  DKKL1  SFRP2  SOST/Sclerostin 
DKK2  FRZB  SFRP4  SOSTDC1 
DKK3  IGFBP4  sFRP-5  WIF1
DKK4  SFRP1 
Wnt Intracellular Signaling
c-Abl/ABL1  CSNK1G1  JNK1  PKC iota 
MASH1/ASCL1  CK2 alpha/CSNK2A1  JNK2  GLRX3/PRKCT 
Calmodulin 1/CALM1  Casein Kinase 2 beta  Calcineurin A/PPP3CA  PRKCZ / PKC zeta 
CAMKI  beta-Catenin  Calcineurin B/PPP3R1  Protein Kinase D2/PRKD2 
CaMKII alpha/CAMK2A  DIXDC1  PKC alpha/PRKCA  PKC nu 
CaMKII beta/CAMK2B  c-Fos  PRKCB  ROCK2 
CaMKII/CAMK2G  c-Jun  PKC delta/PRKCD  TGFB1I1 
Casein Kinase 1 alpha  JunD/Jun-D  PKC epsilon/PRKCE  Ubiquitin/UBB 
Casein Kinase 1 delta  MAP3K7/TAK1  PRKCG/PKCG  VANGL2
CSNK1E  MAPK10/JNK3 
Wnt Ligands (Wnts)
WNT10A  WNT2B  Wnt5b  WNT8A 
WNT10B  WNT3A  Wnt6  WNT8B 
WNT16  Wnt4  Wnt7a  WNT9B
Wnt2  Wnt5a 
Wnt Receptors
FZD1  Frizzled 6  LRP8/ApoER2  ROR2 
Frizzled 10  Frizzled-9/FZD9  LRPAP1  RYK 
Frizzled 2  LRP1  MUSK  ST7 
Frizzled 4  LRP10  ROR1  VANGL2
Frizzled 5  LRP11 
Wnt Signaling Modulators
Biglycan  KREMEN1  RSPO1  Syndecan-2 
DAB2  LEF1  RSPO2  Syndecan-3 
GPC2/Glypican 2  Myocilin  RSPO3  Syndecan-4 
Glypican 3  NDP/EVR2  RSPO4  SHISA4 
Glypican 6/GPC6 NEUROD1  Syndecan-1/CD138  TSPAN12

SUPPORT

outstanding technical support

PRODUCT

we offer a full product guarantee

DELIVERY

we offer free delivery to UK universities and non profit organisations