JAK/STAT-coupled receptors

These JAK/STAT-coupled receptors concern the effects of cytokines the growth hormone somatotropin (GH), erythropoietin (EPO), prolactin (PRL), granulocyte-colony-stimulating-factor (G-CSF), granulocyte and macrophage-colony-stimulating-factor (GM-CSF), leptin, thrombopoi-etin, interferons a, 3 and % and interleukins 2, 3,4, 5, 6, 7, 9,10 and 15. 

Waxman, D.J. and S.J. Frank (2000). Growth Hormone Action Signaling via a JAK/STAT-coupled Receptor. Humana Press, Totowa, pp. 55-83. 

Waxman DJ, Prank SJ (2000) Growth hormone action signaling via a JAK-STAT-coupled receptor. In Conn PM, Means AR (eds) Principle of molecular regulation. Humana Press, Totowa, pp 55-83... 

Cytokine receptors are a group of structurally related receptors, which couple to the JAK-STAT pathway. Cytokine receptors function as homodimers or heterooligomers. They are divided into two main subclasses, class I, which contains receptors for a variety of hematopoietic growth factors and interleukins and class II, which contains receptors for interferons and interleukins 10, 20/24 and 22. 

Besides the cytokine receptors that lack intrinsic kinase activity but have associated JAK kinases, STAT proteins can be activated by a variety of G-protein coupled receptors and growth factor receptors with intrinsic tyrosine kinase activity (for example EGF, PDGF, CSF-1, and angiotensin receptor). Increasing evidence suggests a critical role for STAT family members in oncogenesis and aberrant cell proliferation. Constitutively activated STATs have been found in many transformed cell lines and a wide variety of human tumor entities. Numerous non-receptor tyrosine kinases and viral oncoproteins, such as v-Src, v-Abl, v-Sis, and v-Eyk, have been identified to induce DNA-binding activity of STAT proteins. 

Cytokine receptors that couple to the JAK-STAT Pathway decode the signaling though hematopoietic cytokines (erythropoietin, thrombopoietin, colony-stimulating factors), prolactin, growth hormone, the a-, (3- and y- interferons, and a number of immunomodulatory interleukins [3], They form homodimetic or heterodimeric receptor complexes, which after ligandbinding recruit and activate isotypes of Janus kinases (JAKs). Activated JAKs in turn... 

AII of these hormones act through G protein-coupled receptors except growth hormone and prolactin, which act through JAK/STAT receptors. 

Guillet-Deniau I, Bumol AF, Girard J. Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway. J Biol Chem 1997 272 14,825-14,829. 

Cytokine STAT/JAK pathway Receptor Tyrosine kinase RAS/MAPK pathway G-Protein coupled Receptor pathway ... 

Receptor coupling mechanisms. A number are G-protein coupled (Gi/o), but others involve JAK/STAT, l.e. signalling depends upon receptor association with Janus kinases OAKs), which couple ligand binding to tyrosine phosphorylation of signalling proteins recruited to the receptor complex. 

Figure 8. Schematic of membrane receptors lacking intrinsic enzymatic activity. Intracellular signaling is initiated by coupling of the receptor to an intracellular kinase (e.g JAK kinase). These receptors mediate cytokine signaling (prosurvival protective and maladaptive pathways leading to apoptosis). JAK/STAT signalling is involved in the cellular response to ischemia. Activation of STAT3 reduces ischemia induced apoptosis, whereas activation of STAT1 has the opposite effect.

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