JAK/STAT Pathway
The JAK/STAT pathways mediate signaling from a long list of membrane receptors that include but are not limited to interferon, interleukin, hematopoietic and growth factors receptors.
Signal transducers and activators of transcription (STAT) proteins are a family of transcription factors that bind as homo- or heterodimers to recognition sites such as the c-sis-inducible element (SIE) or g-activated site element (GAS) in gene promoters. STATs are the products of at least seven genes: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B and STAT6. Additional isoforms of these gene products result from alternative gene splicing and post-translational processing. The resulting family of transcription factors generates a wide potential for activation and regulation of specific genes and gene combinations.
STAT proteins are selectively phosphorylated by several families of protein kinases. Cytokines receptors, such as gamma and alpha/beta (a/b) interferon receptors, which lack intrinsic tyrosine kinase activity, rely upon the Janus protein kinase (JAK) family of kinases to phosphorylate STATs. The JAK family includes proteins from at least four genes: JAK1, JAK2, JAK3 and TYK2. JAK1, JAK2 and TYK2 are widely expressed, whereas JAK3 is primarily found in lymphoid and myeloid cells. Certain growth factor receptors, such as the EFG receptor, can activate STAT proteins directly via intrinsic tyrosine kinase or through adaptor captured src family kinase (SFK) protein kinases such as Src kinase. Negative regulation of the JAK/STAT pathways is mediate by members of the suppressor of cytokine signaling (SOCS) family.
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