A kinase independent function for Tec kinase ITK in regulating antigen receptor induced serum response factor activation.

FEBS Letters
Shengli HaoA August

Abstract

The Tec family kinases are critical downstream regulators of antigen receptor signals in lymphocytes. As kinases, they act on critical substrates to regulate signals such as calcium increase leading to activation of transcription factors such as NFAT, NFkappaB and SRF. We now show here that ITK, a member of the Tec family of tyrosine kinases, has a kinase independent function. Mutants of ITK that lack kinase activity or a kinase domain can rescue cells lacking Tec family kinases for antigen receptor induced SRF activation, but not for NFAT, AP-1 or NFkappaB activation. Furthermore, expression of these mutants in WT cells enhanced SRF activation. This kinase independent function required the SH2 domain since a mutant lacking both the kinase and SH2 domains was much less effective at rescuing SRF activation. This kinase-deleted mutant could partially rescue ERK activation, and interact with multiple tyrosine phosphorylated proteins during antigen receptor signaling, suggesting that ITK uses a scaffolding function that regulates signals leading to specific regulation of SRF activation.

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Citations

Mar 5, 2013·The International Journal of Biochemistry & Cell Biology·Weishan HuangAvery August
Apr 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Julie A ReadingerPamela L Schwartzberg
Sep 1, 2009·The Journal of Biological Chemistry·Qian Qi, Avery August
Nov 3, 2010·The Journal of Biological Chemistry·Qian QiAvery August
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Nov 1, 2011·Cell Communication and Signaling : CCS·Jens RauchWalter Kolch
Aug 19, 2009·European Journal of Immunology·Avery August
Jul 13, 2007·Immunological Reviews·Julio Gomez-RodriguezPamela L Schwartzberg
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Jun 1, 2011·Biomolecular Concepts·Qian QiAvery August
Aug 3, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Diane MauriceRichard Treisman
Aug 29, 2007·European Journal of Immunology·Jianfang HuAvery August
Feb 18, 2018·Scientific Reports·Anika HainCarsten Münk
Mar 7, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nisebita SahuAvery August

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