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JAK-STAT Signaling

JAK-STAT signaling in vertebrates relies on a network of protein kinases and transcription factors to integrate signals from various receptor systems. The multitude of stimuli include cytokines, growth factors, and hormones, binding of which ultimately effect processes such as immune response regulation and cell growth, survival, and differentiation.

The highly conserved pathway involves essentially three levels of processing of the incoming information depending on the function of the respective components:

  • Binding of the ligand to the receptor triggers conformational changes of the receptor molecule(s).
  • This steric change of the receptor brings two Janus Kinases (JAK) bound to the receptor or receptor subunits into close proximity, thus enabling trans-phosphorylation. The activated JAKs phosphorylate subsequently additional targets.
  • The major phosphorylation targets are Signal transducer and activator of transcription (STAT). These transcription factors are inactive in the cytoplasm until phosphorylation by JAKs. Once the a conserved tyrosine toward the C-terminus of the STAT has been phosphorylated, it can acts as dimerization interface in conjunction with SH2 domains of another STAT. These activated STAT dimers are then translocated to the nucleus and bind to specific DNA motifs to activate target gene transcription.

Besides, negative regulation of these processes takes place on multiple levels:

  • Suppressors of cytokine signaling (SOCS) gene transcription is stimulated by activated STATs. SOCS inactivate signaling through binding to the phosphorylated JAKs or receptors or facilitate JAK ubiquitination.
  • Protein inhibitor of activated STATs (PIAS) bind to activated STATs and prevent them from binding DNA.
  • Protein tyrosine phosphatases (PTP) reverse the activity of JAKs.

The prototypical JAK-STAT signaling pathway is rather linear. There is however considerable crosstalk with other signaling cascades like MAPK pathways and JAK independent STAT phosphorylation through receptor tyrosine kinase (RTKs).

JAK

Antigens in this category:
JAK1 (Janus Kinase 1): JAK1 antibodies JAK1 ELISA Kits JAK1 Proteins
JAK2 (Janus Kinase 2): JAK2 antibodies JAK2 ELISA Kits JAK2 Proteins
TYK2 (Tyrosine Kinase 2): TYK2 antibodies TYK2 ELISA Kits TYK2 Proteins
JAK3 (Tyrosine-Protein Kinase JAK3): JAK3 antibodies JAK3 ELISA Kits JAK3 Proteins

STAT

Antigens in this category:
STAT1 (Signal Transducer and Activator of Transcription 1, 91kDa): STAT1 antibodies STAT1 ELISA Kits STAT1 Proteins
STAT2 (Signal Transducer and Activator of Transcription 2, 113kDa): STAT2 antibodies STAT2 ELISA Kits STAT2 Proteins
STAT3 (Signal Transducer and Activator of Transcription 3 (Acute-Phase Response Factor)): STAT3 antibodies STAT3 ELISA Kits STAT3 Proteins
STAT4 (Signal Transducer and Activator of Transcription 4): STAT4 antibodies STAT4 ELISA Kits STAT4 Proteins
STAT5A (Signal Transducer and Activator of Transcription 5A): STAT5A antibodies STAT5A ELISA Kits STAT5A Proteins
STAT5B (Signal Transducer and Activator of Transcription 5B): STAT5B antibodies STAT5B ELISA Kits STAT5B Proteins
STAT6 (Signal Transducer and Activator of Transcription 6, Interleukin-4 Induced): STAT6 antibodies STAT6 ELISA Kits STAT6 Proteins

SOCS

Antigens in this category:
SOCS1 (Suppressor of Cytokine Signaling 1): SOCS1 antibodies SOCS1 ELISA Kits SOCS1 Proteins
SOCS2 (Suppressor of Cytokine Signaling 2): SOCS2 antibodies SOCS2 ELISA Kits SOCS2 Proteins
CISH (Cytokine Inducible SH2-Containing Protein): CISH antibodies CISH ELISA Kits CISH Proteins
SOCS3 (Suppressor of Cytokine Signaling 3): SOCS3 antibodies SOCS3 ELISA Kits SOCS3 Proteins
SOCS4 (Suppressor of Cytokine Signaling 4): SOCS4 antibodies SOCS4 ELISA Kits SOCS4 Proteins
SOCS5 (Suppressor of Cytokine Signaling 5): SOCS5 antibodies SOCS5 ELISA Kits SOCS5 Proteins
SOCS6 (Suppressor of Cytokine Signaling 6): SOCS6 antibodies SOCS6 ELISA Kits SOCS6 Proteins

PIAS

Antigens in this category:
PIAS1 (Protein Inhibitor of Activated STAT, 1): PIAS1 antibodies PIAS1 ELISA Kits PIAS1 Proteins
PIAS3 (Protein Inhibitor of Activated STAT, 3): PIAS3 antibodies PIAS3 ELISA Kits PIAS3 Proteins
PIAS2 (Protein Inhibitor of Activated STAT, 2): PIAS2 antibodies PIAS2 ELISA Kits PIAS2 Proteins
PIAS4 (Protein Inhibitor of Activated STAT, 4): PIAS4 antibodies PIAS4 ELISA Kits PIAS4 Proteins

PTP

Antigens in this category:
PTPN11 (Protein tyrosine Phosphatase, Non-Receptor Type 11): PTPN11 antibodies PTPN11 ELISA Kits PTPN11 Proteins
PTPN6 (Protein-tyrosine Phosphatase 1C): PTPN6 antibodies PTPN6 ELISA Kits PTPN6 Proteins
FYN (FYN Oncogene Related To SRC, FGR, YES): FYN antibodies FYN ELISA Kits FYN Proteins
SRC (V-Src Sarcoma (Schmidt-Ruppin A-2) Viral Oncogene Homolog (Avian)): SRC antibodies SRC ELISA Kits SRC Proteins

GP130 family

Antigens in this category:
IL6ST - Interleukin 6 Signal Transducer (Gp130, Oncostatin M Receptor): IL6ST antibodies IL6ST ELISA Kits IL6ST Proteins
IL6R - IL-6 Receptor: IL6R antibodies IL6R ELISA Kits IL6R Proteins
LEP - Leptin: LEP antibodies LEP ELISA Kits LEP Proteins
CTF1 - Cardiotrophin 1: CTF1 antibodies CTF1 ELISA Kits CTF1 Proteins
CNTF (Ciliary Neurotrophic Factor): CNTF antibodies CNTF ELISA Kits CNTF Proteins
CNTFR - CNTF Receptor alpha: CNTFR antibodies CNTFR ELISA Kits CNTFR Proteins
IL11 (Interleukin 11): IL11 antibodies IL11 ELISA Kits IL11 Proteins
IL11RA (Interleukin 11 Receptor, alpha): IL11RA antibodies IL11RA ELISA Kits IL11RA Proteins
IL12 (Interleukin 12): IL12 antibodies IL12 ELISA Kits IL12 Proteins
IL12A - Interleukin 12 alpha: IL12A antibodies IL12A ELISA Kits IL12A Proteins
IL12B - Interleukin 12 beta: IL12B antibodies    
IL12RB1 (Interleukin 12 Receptor beta 1): IL12RB1 antibodies IL12RB1 ELISA Kits IL12RB1 Proteins
IL12RB2 (Interleukin 12 Receptor, beta 2): IL12RB2 antibodies IL12RB2 ELISA Kits IL12RB2 Proteins
IL12B (Interleukin 12b): IL12B antibodies IL12B ELISA Kits IL12B Proteins
Il6ra - IL6RA: Il6ra antibodies Il6ra ELISA Kits  
LEPR - Leptin Receptor: LEPR antibodies LEPR ELISA Kits LEPR Proteins
LIF (Leukemia Inhibitory Factor): LIF antibodies LIF ELISA Kits LIF Proteins
LIFR (Leukemia Inhibitory Factor Receptor alpha): LIFR antibodies LIFR ELISA Kits LIFR Proteins
OSM - Oncostatin M: OSM antibodies OSM ELISA Kits OSM Proteins
OSMR - Oncostatin M Receptor: OSMR antibodies OSMR ELISA Kits OSMR Proteins

Homodimeric receptors

Antigens in this category:
EPO (Erythropoietin): EPO antibodies EPO ELISA Kits EPO Proteins
THPO - Thrombopoietin: THPO antibodies THPO ELISA Kits THPO Proteins
EPOR (Erythropoietin Receptor): EPOR antibodies EPOR ELISA Kits EPOR Proteins
GH1 - Growth Hormone 1: GH1 antibodies GH1 ELISA Kits GH1 Proteins
GH2 - Growth Hormone 2: GH2 antibodies GH2 ELISA Kits GH2 Proteins
GHR - Growth Hormone Receptor: GHR antibodies GHR ELISA Kits GHR Proteins
MPL (Myeloproliferative Leukemia Virus Oncogene): MPL antibodies MPL ELISA Kits MPL Proteins
PRL - Prolactin: PRL antibodies PRL ELISA Kits PRL Proteins
PRLR - Prolactin Receptor: PRLR antibodies PRLR ELISA Kits PRLR Proteins

betaC family

Antigens in this category:
CSF2RB (Colony Stimulating Factor 2 Receptor, Beta, Low-Affinity (Granulocyte-Macrophage)): CSF2RB antibodies CSF2RB ELISA Kits CSF2RB Proteins
CSF2 (Colony Stimulating Factor 2 (Granulocyte-Macrophage)): CSF2 antibodies CSF2 ELISA Kits CSF2 Proteins
Il3 (Interleukin 3 (Colony-Stimulating Factor, Multiple)): Il3 antibodies Il3 ELISA Kits Il3 Proteins
CSF2RA (Colony Stimulating Factor 2 Receptor, Alpha, Low-Affinity (Granulocyte-Macrophage)): CSF2RA antibodies CSF2RA ELISA Kits CSF2RA Proteins
IL3RA (Interleukin 3 Receptor, alpha (Low Affinity)): IL3RA antibodies IL3RA ELISA Kits IL3RA Proteins
IL5 (Interleukin 5): IL5 antibodies IL5 ELISA Kits IL5 Proteins
IL5RA (Interleukin 5 Receptor, alpha): IL5RA antibodies IL5RA ELISA Kits IL5RA Proteins

gammaC family

GPCR

Antigens in this category:
Ang II - Angiotensin II: Ang II antibodies Ang II ELISA Kits Ang II Proteins
GNAQ (Guanine Nucleotide Binding Protein (G Protein), Q Polypeptide): GNAQ antibodies GNAQ ELISA Kits GNAQ Proteins
HTR1A - Serotonin Receptor 1A: HTR1A antibodies HTR1A ELISA Kits HTR1A Proteins
HTR1B - 5HT1B Receptor: HTR1B antibodies HTR1B ELISA Kits HTR1B Proteins
HTR2A - 5-Hydroxytryptamine (serotonin) Receptor 2A, G Protein-Coupled: HTR2A antibodies HTR2A ELISA Kits  
HTR7 (5-Hydroxytryptamine (serotonin) Receptor 7 (Adenylate Cyclase-Coupled)): HTR7 antibodies    
HTR1F (5-Hydroxytryptamine Receptor 1F): HTR1F antibodies    
AGTR1 - Angiotensin II Type-1 Receptor: AGTR1 antibodies AGTR1 ELISA Kits AGTR1 Proteins
Ang II/III - Angiotensin II/III: Ang II/III antibodies    
AGT (Angiotensinogen (serpin Peptidase Inhibitor, Clade A, Member 8)): AGT antibodies AGT ELISA Kits AGT Proteins
HTR1D (found in nociceptors throughout the body [RGD, Feb 2006].."): HTR1D antibodies HTR1D ELISA Kits HTR1D Proteins
HTR1E - Serotonin Receptor 1E: HTR1E antibodies   HTR1E Proteins
HTR1F - Serotonin Receptor 1F: HTR1F antibodies HTR1F ELISA Kits  
HTR2B - Serotonin Receptor 2B: HTR2B antibodies HTR2B ELISA Kits HTR2B Proteins
HTR4 - Serotonin Receptor 4: HTR4 antibodies HTR4 ELISA Kits HTR4 Proteins
HTR5A - Serotonin Receptor 5A: HTR5A antibodies HTR5A ELISA Kits HTR5A Proteins
HTR6 - Serotonin Receptor 6: HTR6 antibodies   HTR6 Proteins
HTR7 - Serotonin Receptor 7: HTR7 antibodies HTR7 ELISA Kits HTR7 Proteins

Interferons

Antigens in this category:
IFNAR1 (Interferon (Alpha, beta and Omega) Receptor 1): IFNAR1 antibodies IFNAR1 ELISA Kits IFNAR1 Proteins
IFNA2 (Interferon, alpha 2): IFNA2 antibodies IFNA2 ELISA Kits IFNA2 Proteins
IFNA (Interferon alpha): IFNA antibodies IFNA ELISA Kits IFNA Proteins
IFNAR2 (Interferon alpha/beta Receptor 2): IFNAR2 antibodies IFNAR2 ELISA Kits IFNAR2 Proteins
IRF9 (Interferon Regulatory Factor 9): IRF9 antibodies IRF9 ELISA Kits IRF9 Proteins
IFNA1 (Interferon, alpha 1): IFNA1 antibodies   IFNA1 Proteins
IFNa10 - IFNA10: IFNa10 antibodies IFNa10 ELISA Kits IFNa10 Proteins
IFNA13 (Interferon, alpha 13): IFNA13 antibodies IFNA13 ELISA Kits IFNA13 Proteins
IFNa14 (Interferon, alpha 14): IFNa14 antibodies   IFNa14 Proteins
IFNA16 (Interferon, alpha 16): IFNA16 antibodies   IFNA16 Proteins
IFNa17 - IFNA17: IFNa17 antibodies   IFNa17 Proteins
IFNa21 - IFNA21: IFNa21 antibodies IFNa21 ELISA Kits IFNa21 Proteins
IFNa4 - IFNA4: IFNa4 antibodies IFNa4 ELISA Kits IFNa4 Proteins
IFNA5 (Interferon, alpha 5): IFNA5 antibodies IFNA5 ELISA Kits IFNA5 Proteins
IFNA6 (Interferon, alpha 6): IFNA6 antibodies IFNA6 ELISA Kits IFNA6 Proteins
IFNa7 - IFNA7: IFNa7 antibodies IFNa7 ELISA Kits IFNa7 Proteins
IFNA8 (Interferon, alpha 8): IFNA8 antibodies   IFNA8 Proteins
IFNB1 (Interferon, beta 1, Fibroblast): IFNB1 antibodies IFNB1 ELISA Kits IFNB1 Proteins