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- Title
A new protein containing an SH2 domain that inhibits JAK kinases.
- Authors
Endo, T A; Masuhara, M; Yokouchi, M; Suzuki, R; Sakamoto, H; Mitsui, K; Matsumoto, A; Tanimura, S; Ohtsubo, M; Misawa, H; Miyazaki, T; Leonor, N; Taniguchi, T; Fujita, T; Kanakura, Y; Komiya, S; Yoshimura, A
- Abstract
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.
- Publication
Nature, 1997, Vol 387, Issue 6636, p921
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/43213