JCB logo
MBoC5 from Garland Science
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 28 March 2005. doi:10.1083/jcb.200405116
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 7, 1099-1108
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 878K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Defilippi, P.
Right arrow Articles by Brizzi, M. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Defilippi, P.
Right arrow Articles by Brizzi, M. F.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
Medline Plus Health Information
*Dietary Proteins
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?

Article

 ß1 integrin and IL-3R coordinately regulate STAT5 activation and anchorage-dependent proliferation

Paola Defilippi1, Arturo Rosso2, Patrizia Dentelli2, Cristina Calvi2, Giovanni Garbarino2, Guido Tarone1, Luigi Pegoraro2, and Maria Felice Brizzi2

1 Department of Genetics, Biology and Biochemistry
2 Department of Internal Medicine, University of Torino, 10126, Torino, Italy

Correspondence to P. Defilippi: paola.defilippi{at}unito.it; or M.F. Brizzi: mariafelice.brizzi{at}unito.it

We previously demonstrated that integrin-dependent adhesion activates STAT5A, a well known target of IL-3–mediated signaling. Here, we show that in endothelial cells the active ß1 integrin constitutively associates with the unphosphorylated IL-3 receptor (IL-3R) ß common subunit. This association is not sufficient for activating downstream signals. Indeed, only upon fibronectin adhesion is Janus Kinase 2 (JAK2) recruited to the ß1 integrin–IL-3R complex and triggers IL-3R ß common phosphorylation, leading to the formation of docking sites for activated STAT5A. These events are IL-3 independent but require the integrity of the IL-3R ß common. IL-3 treatment increases JAK2 activation and STAT5A and STAT5B tyrosine and serine phosphorylation and leads to cell cycle progression in adherent cells. Expression of an inactive STAT5A inhibits cell cycle progression upon IL-3 treatment, identifying integrin-dependent STAT5A activation as a priming event for IL-3–mediated S phase entry. Consistently, overexpression of a constitutive active STAT5A leads to anchorage-independent cell cycle progression. Therefore, these data provide strong evidence that integrin-dependent STAT5A activation controls IL-3–mediated proliferation.

Abbreviations used in this paper: EMSA, electrophoretic mobility shift assay; FN, fibronectin; IB, immunoblotted; IP, immunoprecipitated; JAK2, Janus Kinase 2; SIE, Sis-inducible element of c-fos.


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 | Help | Feedback | Subscriptions | Archive | Search | Table of Contents