JBC Anatrace, Inc.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M311622200 on April 6, 2004

J. Biol. Chem., Vol. 279, Issue 23, 24899-24905, June 4, 2004
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
279/23/24899    most recent
M311622200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Garnovskaya, M. N.
Right arrow Articles by Raymond, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garnovskaya, M. N.
Right arrow Articles by Raymond, J. R.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Mitogen-induced Rapid Phosphorylation of Serine 795 of the Retinoblastoma Gene Product in Vascular Smooth Muscle Cells Involves ERK Activation*

Maria N. Garnovskaya{ddagger}, Yurii V. Mukhin, Tamara M. Vlasova, Jasjit S. Grewal, Michael E. Ullian, Baby G. Tholanikunnel, and John R. Raymond

From the Medical and Research Services of the Ralph H. Johnson Veterans Affairs Medical Center and Department of Medicine (Nephrology Division) of the Medical University of South Carolina, Charleston, South Carolina 29425

We examined the relationship between mitogen-activated MEK (mitogen and extracellular signal-regulated protein kinase kinase) and phosphorylation of the gene product encoded by retinoblastoma (hereafter referred to as Rb) in vascular smooth muscle cells. Brief treatment of the cells with 100 nM angiotensin II or 1 µM serotonin resulted in serine phosphorylation of Rb that was equal in magnitude to that induced by treating cells for 20 h with 10% fetal bovine serum ({approx}3 x basal). There was no detectable rapid phosphorylation of two close cousins of Rb, p107 and p130. Phosphorylation state-specific antisera demonstrated that the rapid phosphorylation occurred on Ser795, but not on Ser249, Thr252, Thr373, Ser780, Ser807, or Ser811. Phosphorylation of Rb Ser795 peaked at 10 min, lagging behind phosphorylation of MEK and ERK (extracellular signal-regulated protein kinase). Rb Ser795 phosphorylation could be blocked by PD98059, a MEK inhibitor, and greatly attenuated by apigenin, an inhibitor of the Ras -> Raf -> MEK -> ERK pathway. The effect also appears to be mediated by CDK4. Immunoprecipitation/immunoblot studies revealed that serotonin and angiotensin II induced complex formation between CDK4, cyclin D1, and phosphorylated ERK. These studies show a rapid, novel, and selective phosphorylation of Rb Ser795 by mitogens and demonstrate an unexpected rapid linkage between the actions of the Ras -> Raf -> MEK -> ERK pathway and the phosphorylation state of Rb.


Received for publication, October 23, 2003 , and in revised form, April 2, 2004.

* This work was supported by Department of Veterans Affairs Merit Awards (to M. N. G. and J. R. R.) and a Research Enhancement Award Program (to J. R. R., Y. V. M., and M. N. G.), National Institutes of Health Grants RO1-DK52448 and RO1-GM63909 (to J. R. R.) and K01-DK02694 (to Y. V. M.), American Heart Association grants (to Y. V .M., J. S. G., and M. E. U.), a laboratory endowment jointly supported by the M.U.S.C. Division of Nephrology and Dialysis Clinics, Inc. (to J. R. R.), and a M.U.S.C. University Research Foundation award (to M. N. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed: Medical University of South Carolina, 96 Jonathan Lucas St., Rm. 829 CSB, P. O. Box 250623, Charleston, SC 29425-2227. Tel.: 843-876-5128 or 843-789-6774; Fax: 843-876-5129 or 843-792-8399; E-mail: garnovsk{at}musc.edu.


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


This article has been cited by other articles:


Home page
J. Biol. Chem.Home page
J. Guo, G. Sheng, and B. W. Warner
Epidermal Growth Factor-induced Rapid Retinoblastoma Phosphorylation at Ser780 and Ser795 Is Mediated by ERK1/2 in Small Intestine Epithelial Cells
J. Biol. Chem., October 28, 2005; 280(43): 35992 - 35998.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
E. Gabele, S. Reif, S. Tsukada, R. Bataller, Y. Yata, T. Morris, L. W. Schrum, D. A. Brenner, and R. A. Rippe
The Role of p70S6K in Hepatic Stellate Cell Collagen Gene Expression and Cell Proliferation
J. Biol. Chem., April 8, 2005; 280(14): 13374 - 13382.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.