1998 Fiscal Year Final Research Report Summary
The role of kinase-like domain and N-terminal domain of Jak2 in hematopoietic cell growth
| Project/Area Number |
09671118
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Ehime University |
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Principal Investigator |
SAKAI Ikuya Ehime University School of Medicine Assistant Professor, 医学部, 助手 (10205700)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Jak kinase / kinase-like domain / N-terminal domain / CD16 / CD7 / IL-3 / Tcl-1 / STAT |
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| Research Abstract |
Jak kinase family (Jakl, 2,3, and tyk2) consists of kinase-like domain, which has kinase structure but doesn't has kinase activity, and N-terminal domain which is conserved among Jak family member, in addition to the kinase domain. To investigate the role of these domain, I deleted the kinase-like domain, N-terminal domain and both of them of the Jak2 and fused theses mutants with CDl6/CD7, expressed, activated and analyzed the difference of these signals. Deletion of either kinase-like domain or N-terminal domain gave the constitutive activation of Jak2 and both deletion gave hyper activation of Jak2 and 1L3 dependent cell line which express this protein grew without IL-3 and prevented apoptosis. These results suggested that kinase-like domain and N-terminal domain might function as a regulatory region that inhibits Jak2 kinase activity. I explore the protein which bind to the N-terminal domain of the Jak2 using yeast two hybrid system and identified onco-gene TcI-l. GST-Tcl-l bind Jak2 and Jak3 in vitro.
I investigated the relation between activation of STAT and activation of Jak kinases in T cell line and T cell tumor which sowed constitutive activation of STAT.Although constitutive activation of STAT3 was detected in these cells but activations of Jak kinases did not related of activation of STAT3 and STAT3 might be regulated by other kinases.
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