Protein kinase Cθ C2 domain is a phosphotyrosine binding module that plays a key role in its activation

Robert Stahelin, Kok Fai Kong, Sumita Raha, Wen Tian, Heather R. Melowic, Katherine E. Ward, Diana Murray, Amnon Altman, Wonhwa Cho

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Protein kinase Cθ (PKCθ) is a novel PKC that plays a key role in T lymphocyte activation. To understand how PKCθ is regulated in T cells, we investigated the properties of its N-terminal C2 domain that functions as an autoinhibitory domain. Our measurements show that a Tyr(P)-containing peptide derived from CDCP1 binds the C2 domain of PKCθ with high affinity and activates the enzyme activity of the intact protein. The Tyr(P) peptide also binds the C2 domain of PKCθ tightly, but no enzyme activation was observed with PKCδ. Mutations of PKCθ-C2 residues involved in Tyr(P) binding abrogated the enzyme activation and association of PKCθ with Tyr-phosphorylated full-length CDCP1 and severely inhibited the T cell receptor/CD28-mediated activation of a PKCθ-dependent reporter gene in T cells. Collectively, these studies establish the C2 domain of PKCθ as a Tyr(P)-binding domain and suggest that the domain may play a major role in PKCθ activation via its Tyr(P) binding.

Original languageEnglish
Pages (from-to)30518-30528
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number36
DOIs
StatePublished - Aug 31 2012

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Phosphotyrosine
Protein Kinase C
Chemical activation
T-cells
Enzyme Activation
T-Lymphocytes
C2 Domains
Enzyme activity
Enzymes
Lymphocyte Activation
T-Cell Antigen Receptor
Reporter Genes
Genes
Association reactions

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Protein kinase Cθ C2 domain is a phosphotyrosine binding module that plays a key role in its activation. / Stahelin, Robert; Kong, Kok Fai; Raha, Sumita; Tian, Wen; Melowic, Heather R.; Ward, Katherine E.; Murray, Diana; Altman, Amnon; Cho, Wonhwa.

In: Journal of Biological Chemistry, Vol. 287, No. 36, 31.08.2012, p. 30518-30528.

Research output: Contribution to journalArticle

Stahelin, R, Kong, KF, Raha, S, Tian, W, Melowic, HR, Ward, KE, Murray, D, Altman, A & Cho, W 2012, 'Protein kinase Cθ C2 domain is a phosphotyrosine binding module that plays a key role in its activation', Journal of Biological Chemistry, vol. 287, no. 36, pp. 30518-30528. https://doi.org/10.1074/jbc.M112.391557
Stahelin, Robert ; Kong, Kok Fai ; Raha, Sumita ; Tian, Wen ; Melowic, Heather R. ; Ward, Katherine E. ; Murray, Diana ; Altman, Amnon ; Cho, Wonhwa. / Protein kinase Cθ C2 domain is a phosphotyrosine binding module that plays a key role in its activation. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 36. pp. 30518-30528.
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