Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in normal prostatic epithelium and cancer

Jian Zhou, Jessica Scholes, Jer Tsong Hsieh

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

DOC-2/DAB2 is a potent tumor suppressor in many cancer types including prostate cancer. In prostate cancer, expression of DOC-2/DAB2 can inhibit its growth. Our recent studies demonstrate that DOC-2/DAB2 can suppress both protein kinase C and peptide growth factor-elicited signal pathways via the Ras-mitogen-activated protein kinase pathway. In this study, we further showed that the proline-rich domain of DOC-2/DAB2 could also interact with proteins containing the Srchomology 3 domain, such as Src and Fgr. The binding of c-Src to DOC-2/DAB2 was enhanced in cells treated with growth factor, and this interaction resulted in c-Src inactivation. The c-Src inactivation was evidenced by the decreased tyrosine 416 phosphorylation of c-Src and reduced downstream effector activation. It appears that DOC-2/DAB2 can bind to Src homology 3 domain of c-Src and maintain it in an inactive conformation. Thus, this study provides a new mechanism for modulating c-Src in prostatic epithelium and cancer.

Original languageEnglish (US)
Pages (from-to)6936-6941
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number9
DOIs
StatePublished - Feb 28 2003

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Prostatic Neoplasms
Intercellular Signaling Peptides and Proteins
Epithelium
Phosphorylation
C-Peptide
Mitogen-Activated Protein Kinases
Proline
Protein Kinase C
Tyrosine
Conformations
Tumors
Chemical activation
src Homology Domains
Signal Transduction
Proteins
Growth
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in normal prostatic epithelium and cancer. / Zhou, Jian; Scholes, Jessica; Hsieh, Jer Tsong.

In: Journal of Biological Chemistry, Vol. 278, No. 9, 28.02.2003, p. 6936-6941.

Research output: Contribution to journalArticle

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AB - DOC-2/DAB2 is a potent tumor suppressor in many cancer types including prostate cancer. In prostate cancer, expression of DOC-2/DAB2 can inhibit its growth. Our recent studies demonstrate that DOC-2/DAB2 can suppress both protein kinase C and peptide growth factor-elicited signal pathways via the Ras-mitogen-activated protein kinase pathway. In this study, we further showed that the proline-rich domain of DOC-2/DAB2 could also interact with proteins containing the Srchomology 3 domain, such as Src and Fgr. The binding of c-Src to DOC-2/DAB2 was enhanced in cells treated with growth factor, and this interaction resulted in c-Src inactivation. The c-Src inactivation was evidenced by the decreased tyrosine 416 phosphorylation of c-Src and reduced downstream effector activation. It appears that DOC-2/DAB2 can bind to Src homology 3 domain of c-Src and maintain it in an inactive conformation. Thus, this study provides a new mechanism for modulating c-Src in prostatic epithelium and cancer.

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