SOCS-1/JAB/SSI-1 Can Bind to and Suppress Tec Protein-tyrosine Kinase*
- Ken-ichi Ohya‡,
- Sachiko Kajigaya§,
- Yoshihiro Yamashita¶,
- Akira Miyazato‖,
- Kiyohiko Hatake‖,
- Yasusada Miura‖,
- Uichi Ikeda‡,
- Kazuyuki Shimada‡,
- Keiya Ozawa¶ and
- Hiroyuki Mano¶**
- From the Divisions of ‡Cardiology and‖Hematology and the ¶Department of Molecular Biology, Jichi Medical School, 3311-1 Yakushiji, Kawachi-gun, Tochigi 329–04, Japan and the §Hematology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892
Abstract
Tec is the prototype of a recently emerging subfamily among nonreceptor type protein-tyrosine kinases and is known to become tyrosine-phosphorylated and activated by a wide range of cytokine stimulations in hematopoietic cells. Although Tec was recently shown to be involved in the cytokine-driven activation mechanism of c-fos transcription, it is yet obscure how Tec relays the signals from cell surface receptors to the nucleus. To identify signaling molecules acting downstream of Tec, we have looked for Tec-interacting proteins (TIPs) by using the yeast two-hybrid system. Here we report the identification and characterization of a novel protein, TIP3, which has been simultaneously identified by other groups as SOCS-1, JAB, or SSI-1. TIP3 carries one Src homology 2 domain with a sequence similarity to that of CIS. In 293 cells, TIP3 associates with Tec and suppresses its kinase activity. Interestingly, TIP3 can also down-regulate the activity of Jak2 but not that of Lyn. We propose that SOCS-1/JAB/SSI-1/TIP3 is a novel type of negative regulator to a subset of protein-tyrosine kinases.
Footnotes
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↵* This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture, Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AB000734.
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↵** To whom correspondence should be addressed: Dept. of Molecular Biology, Jichi Medical School, 3311-1 Yakushiji, Kawachi-gun, Tochigi 329–04, Japan. Tel.: 81-285-44-2111; Fax: 81-285-44-8675; E-mail:hmano{at}jichi.ac.jp.
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↵1 The abbreviations used are: PTK, protein-tyrosine kinase; IL, interleukin; TIP, Tec-interacting protein; SH, Src homology; HIV, human immunodeficiency virus; GST, glutathioneS-transferase; GM-CSF, granulocyte-macrophage colony-stimulating factor; αP-Tyr Ab, anti-phosphotyrosine antibody; Tricine,N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine.
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↵2 Y. Yamashita, S. Watanabe, A. Miyazato, K. Ohya, U. Ikeda, K. Shimada, N. Komatsu, K. Hatake, Y. Miura, K. Ozawa, and H. Mano, submitted for publication.
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↵3 H. Mano, K. Ohya, A. Miyazato, Y. Yamashita, W. Ogawa, J. Inazawa, U. Ikeda, K. Shimada, N. Komatsu, K. Hatake, Y. Miura, M. Kasuga, K. Ozawa, and S. Kajigaya, submitted for publication.
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- Received June 19, 1997.
- Revision received August 12, 1997.
