Tyrosine phosphorylation of c-ErbB-2 is regulated by the cellular form of prostatic acid phosphatase in human prostate cancer cells

Tzu Ching Meng, Ming-Fong Lin

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Human prostatic acid phosphatase (PAcP) is a prostate epithelium- specific differentiation antigen. In prostate carcinomas, the cellular PAcP is decreased. We investigated its functional role in these cells. Several lines of evidence support the hypothesis that cellular PAcP functions as a neutral protein-tyrosine phosphatase and is involved in regulating prostate cell growth. In this study, we identify its in vivo substrate. Our results demonstrated that, in different human prostate cancer cell lines, the phosphotyrosine (Tyr(P)) level of a 185-kDa phosphoprotein (pp185) inversely correlates with the cellular activity of PAcP. On SDS-PAGE, this pp185 comigrates with the c-ErbB-2 oncoprotein. Immunodepletion experiments revealed that c-ErbB-2 protein is the major pp185 in cells. Results from subclones of LNCaP cells indicated the lower the cellular PAcP activity, the higher the Tyr(P) levels of c-ErbB-2. This inverse correlation was further observed in PAcP cDNA-transfected cells. In clone 33 LNCaP cells, L-(+)- tartrate suppresses the cellular PAcP activity and causes an elevated Tyr(P) level of c-ErbB-2 protein. Epidermal growth factor stimulates the proliferation of LNCaP cells, which concurs with a decreased cellular PAcP activity as well as an increased Tyr(P) level of c-ErbB-2. Biochemically, PAcP dephosphorylates c-ErbB-2 at pH 7.0. The results thus suggest that cellular PAcP down-regulates prostate cell growth by dephosphorylating Tyr(P) on c-ErbB-2 oncoprotein in those cells.

Original languageEnglish (US)
Pages (from-to)22096-22104
Number of pages9
JournalJournal of Biological Chemistry
Volume273
Issue number34
DOIs
StatePublished - Aug 21 1998

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Phosphorylation
Tyrosine
Prostatic Neoplasms
Cells
ErbB-2 Receptor
Prostate
Oncogene Proteins
Cell growth
prostatic acid phosphatase
Phosphotyrosine
Protein Tyrosine Phosphatases
Phosphoproteins
Differentiation Antigens
Prostate-Specific Antigen
Growth
Epidermal Growth Factor
Polyacrylamide Gel Electrophoresis
Down-Regulation
Epithelium
Complementary DNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tyrosine phosphorylation of c-ErbB-2 is regulated by the cellular form of prostatic acid phosphatase in human prostate cancer cells. / Meng, Tzu Ching; Lin, Ming-Fong.

In: Journal of Biological Chemistry, Vol. 273, No. 34, 21.08.1998, p. 22096-22104.

Research output: Contribution to journalArticle

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