Cross-regulation of JAK and Src kinases.
Members of the Janus kinase (JAK) family, JAK1, JAK2, JAK3 and Tyk2 are intimately involved in the signalling events initiated by cytokines activating cell surface receptors. They are responsible for phosphorylating these receptors, which create docking sites for downstream molecules such as the signal transducer and activator of transcription family members. In addition, cytokine receptors associate with members of the Src family kinase (SFK). JAKs and SFK work in concert to activate many of the signalling molecules, with both kinase families required for optimal transmission of intracellular signals. JAKs and SFK are also required for the activation and recruitment of negative regulators of cytokine signalling, e.g., protein tyrosine phosphatases (PTPs) and suppressors of cytokine signalling. Aberrant activity of the JAK-Src kinase duet can result in hemopoietic abnormalities including leukaemia. Additionally, the recent identification of a somatic JAK2 mutation as the cause of polycythema vera, further highlights the clinical importance of these molecules.
Ingley
Evan
E
Western Australian Institute for Medical Research and UWA Centre for Medical Research, The University of Western Australia, Laboratory for Cancer Medicine, Perth, WA, Australia.
Klinken
S Peter
SP
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D009154:Mutation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D019061:src-Family Kinases / Q000502:physiology*
D016207:Cytokines; D011518:Proto-Oncogene Proteins; D050791:STAT Transcription Factors; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D019061:src-Family Kinases