A new protein containing an SH2 domain that inhibits JAK kinases

Takaho A. Endo, Masaaki Masuhara, Masahiro Yokouchi, Ritsu Suzuki, Hiroshi Sakamoto, Kaoru Mitsui, Akira Matsumoto, Shyu Tanimura, Motoaki Ohtsubo, Hiroyuki Misawa, Tadaaki Miyazaki, Nogueira Leonor, Tadatsugu Taniguchi, Takashi Fujita, Yuzuru Kanakura, Seturo Komiya, Akihiko Yoshimura

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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 signaling 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.

Original languageEnglish
Pages (from-to)921-924
Number of pages4
JournalNature
Volume387
Issue number6636
DOIs
Publication statusPublished - 1997 Jun 26
Externally publishedYes

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ASJC Scopus subject areas

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Cite this

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. (1997). A new protein containing an SH2 domain that inhibits JAK kinases. Nature, 387(6636), 921-924. https://doi.org/10.1038/43213