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

Shengli Hao, Qian Qi, Jianfang Hu, Avery August

Research output: Contribution to journalArticle

19 Citations (Scopus)

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, NFκB 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 NFκB 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.

Original languageEnglish (US)
Pages (from-to)2691-2697
Number of pages7
JournalFEBS Letters
Volume580
Issue number11
DOIs
StatePublished - May 15 2006

Fingerprint

Serum Response Factor
Antigen Receptors
Phosphotransferases
Chemical activation
src Homology Domains
Transcription Factor AP-1
Tec protein-tyrosine kinase
Lymphocytes
Tyrosine
Transcription Factors
Protein-Tyrosine Kinases
Calcium

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Hao, Shengli ; Qi, Qian ; Hu, Jianfang ; August, Avery. / A kinase independent function for Tec kinase ITK in regulating antigen receptor induced serum response factor activation. In: FEBS Letters. 2006 ; Vol. 580, No. 11. pp. 2691-2697.
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A kinase independent function for Tec kinase ITK in regulating antigen receptor induced serum response factor activation. / Hao, Shengli; Qi, Qian; Hu, Jianfang; August, Avery.

In: FEBS Letters, Vol. 580, No. 11, 15.05.2006, p. 2691-2697.

Research output: Contribution to journalArticle

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