| First Author | Endo TA | Year | 1997 |
| Journal | Nature | Volume | 387 |
| Issue | 6636 | Pages | 921-4 |
| PubMed ID | 9202126 | Mgi Jnum | J:43733 |
| Mgi Id | MGI:1098502 | Doi | 10.1038/43213 |
| Citation | Endo TA, et al. (1997) A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387(6636):921-4 |
| abstractText | The proliferation and differentiation of cells of many lineages are regulated by secreted proteins known as cytokines. Cytokines exert their biological effect through binding to cell-surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases. Cytokine-induced receptor dimerization leads to the activation of JAKs, rapid tyrosine-phosphorylation of the cytoplasmic domains, and subsequent recruitment of various signalling proteins, including members of the STAT family of transcription factors, to the receptor complex. Using the yeast two-hybrid system, we have now isolated a new SH2-domain-containing protein, JAB, which is a JAK-binding protein that interacts with the Jak2 tyrosine-kinase JH1 domain. JAB is structurally related to CIS, a cytokine-inducible SH2 protein. Interaction of JAB with Jak1, Jak2 or Jak3 markedly reduces their tyrosine-kinase activity and suppresses the tyrosine-phosphorylation and activation of STATs. JAB and CIS appear to function as negative regulators in the JAK signalling pathway. |
