HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ouyang, X. Articles by Epstein, R. Search for Related Content PubMed PubMed Citation Articles by Ouyang, X. Articles by Epstein, R. Social Bookmarking                      What's this?

Volume 271, Number 36, Issue of September 6, 1996 pp. 21786-21792
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Human Cancer Cells Exhibit Protein Kinase C-dependent c-erbB-2 Transmodulation That Correlates with Phosphatase Sensitivity and Kinase Activity

(Received for publication, April 24, 1996, and in revised form, June 27, 1996)

Xiaomei Ouyang , Tim Gulliford , Hongyi Zhang , Guo Cai Huang and Richard Epstein ^''

From the  Division of Cell, Molecular and Oncology Research, Charing Cross and Westminster Medical School, University of London and ^'' Cancer Research Campaign Laboratories, Department of Medical Oncology and  Department of Biochemistry, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, United Kingdom

The c-erbB-2 receptor tyrosine kinase is often overexpressed in human tumors, but the functional implications of this phenotype remain unclear. We previously used phosphorylation-specific antibodies to define major differences in c-erbB-2 tyrosine kinase activity between overexpressing human tumor cell lines (Epstein, R. J., Druker, B. J., Roberts, T. M., and Stiles, C. D. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 10435-10439). Here we extend this approach to define the relationship between c-erbB-2 tyrosine phosphorylation and protein kinase C (PKC)-dependent transmodulation. Phosphorylation-specific antibodies to the juxtamembrane PKC site Thr⁶⁸⁶ recognize tyrosine-dephosphorylated wild-type c-erbB-2 following G8/DHFR 3T3 cell treatment with PKC agonists. B104-1-1 cells transformed by activated c-erbB-2 express a subset of tyrosine-phosphorylated receptors that are homologously phosphorylated on Thr⁶⁸⁶, indicating that Thr⁶⁸⁶ phosphorylation alone is insufficient to abrogate receptor tyrosine phosphorylation. Similarly, the c-erbB-2-overexpressing human cancer cell lines SK-Ov-3 and BT-474 express constitutively Thr⁶⁸⁶-phosphorylated receptors. SK-Ov-3 cells express predominantly kinase-inactive c-erbB-2 that is heavily Thr⁶⁸⁶-phosphorylated, indicating that Thr⁶⁸⁶ phosphorylation in this line is heterologous in origin. In contrast, BT-474 cells express constitutively autophosphorylated c-erbB-2 despite Thr⁶⁸⁶ phosphorylation. These results indicate that Thr⁶⁸⁶ phosphorylation does not directly abolish c-erbB-2 activity and suggest that such phosphorylation reflects constitutive PKC activity induced by either receptor-activating mutations or heterologous growth factors. The latter possibility suggests in turn that c-erbB-2 interacts in an as yet undefined way with heterologous growth factor receptors in human tumor cells.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. W. Thiel and G. Carpenter Epidermal growth factor receptor juxtamembrane region regulates allosteric tyrosine kinase activation PNAS, December 4, 2007; 104(49): 19238 - 19243. [Abstract] [Full Text] [PDF]

				H. Zhang, Y. Li, T. Peng, M. Aasa, L. Zhang, Y. Yang, and L. C. Archard Localization of Enteroviral Antigen in Myocardium and Other Tissues from Patients with Heart Muscle Disease by an Improved Immunohistochemical Technique J. Histochem. Cytochem., May 1, 2000; 48(5): 579 - 584. [Abstract] [Full Text]

				K. Szepeshazi, A. V. Schally, G. Halmos, N. Lamharzi, K. Groot, and J. E. Horvath A single in vivo administration of bombesin antagonist RC-3095 reduces the levels and mRNA expression of epidermal growth factor receptors in MXT mouse mammary cancers PNAS, September 30, 1997; 94(20): 10913 - 10918. [Abstract] [Full Text] [PDF]