Metallothionein 2A interacts with the kinase domain of PKCμ in prostate cancer

Prema S. Rao, Meena Jaggi, David J. Smith, George P. Hemstreet, K. C. Balaji

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Prostate cancer (PC) patients die from progression to androgen independence (AI) and chemoresistance (CR). Protein kinase Cμ (PKCμ) a novel member of the PKC family of signal transduction proteins is downregulated in AI PC. Studying PKCμ interactors in the yeast two-hybrid system identified metallothionein 2A (MT 2A) as an interactor of PKCμ kinase domain (KD) in PC, which was quantified by β-gal assay, confirmed in PC cells by immunoprecipitation, and PKCμ-MT 2A co-localization in vivo by immunofluorescence studies. PKCμ domain interaction studies revealed that MT 2A interacted strongly with KD, relatively weakly with C1, and failed to interact with C2, PH or kinase mutant domains. Peptide library and in silico analysis strongly suggest that MT 2A is a novel substrate of PKCμ and our data indicate that the PKCμ-MT 2A interaction depends on PKCμ kinase activity. Because metallothioneins are associated with cell proliferation and CR, the PKCμ-MT 2A interaction may contribute to CR and/or AI in PC.

Original languageEnglish (US)
Pages (from-to)1032-1038
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume310
Issue number3
DOIs
StatePublished - Oct 24 2003
Externally publishedYes

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Metallothionein
Protein Kinase C
Prostatic Neoplasms
Phosphotransferases
Androgens
Peptide Library
Signal transduction
Two-Hybrid System Techniques
protein kinase C kinase
Cell proliferation
Hybrid systems
Immunoprecipitation
Computer Simulation
Yeast
Fluorescent Antibody Technique
Assays
Signal Transduction
Down-Regulation
Cell Proliferation
Substrates

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Metallothionein 2A interacts with the kinase domain of PKCμ in prostate cancer. / Rao, Prema S.; Jaggi, Meena; Smith, David J.; Hemstreet, George P.; Balaji, K. C.

In: Biochemical and Biophysical Research Communications, Vol. 310, No. 3, 24.10.2003, p. 1032-1038.

Research output: Contribution to journalArticle

Rao, Prema S. ; Jaggi, Meena ; Smith, David J. ; Hemstreet, George P. ; Balaji, K. C. / Metallothionein 2A interacts with the kinase domain of PKCμ in prostate cancer. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 310, No. 3. pp. 1032-1038.
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