![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on January 1, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 23, 2002
Revised on September 25, 2002
Accepted on October 3, 2002
1 Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain
2 Department of Pathology, Uniformed Services University of the Health Sciences, USA
* Corresponding author. E-mail address: jclacal{at}iib.uam.es.
The involvement of Rho GTPases in signal transduction pathways leading to transcription activation is one of the major roles of this family of GTPases. Thus, the identification of transcription factors regulated by Rho GTPases as well as the understanding of the mechanisms of their activation and its biological outcome is of great interest. We provide here evidence that Rho GTPases modulate Stat5a, a transcription factor of the family of Signal Transducers and Activators of Transcription. RhoA triggers tyrosine phosphorylation (Y696) of Stat5a via a JAK2-dependent mechanism, and promotes DNA-binding activity of Stat5a. Tyrosine phosphorylation of Stat5a is also stimulated physiologically by LPA in a Rho-dependent manner. Simultaneously, RhoA reduces serine phosphorylation of Stat5a at both serine residues S726 and S780, resulting in a further increase of activity as defined by mutagenesis experiments. Furthermore, serine dephosphorylation of Stat5a by RhoA does not take place by downmodulation of either JNK1, MEK1 or p38 MAP kinases, as determined by transfection experiments or chemical inhibition of both MEK1, p38 and JNK serine kinases. Thus, RhoA regulates Stat5a via tyrosine phosphorylation, and by a yet to be determined novel downmodulating pathway that involves serine dephosphorylation. At last we provide evidence for a role of Stat5a in RhoA-induced epithelial to mesenchymal transition (EMT) with concomitant increase in vimentin expression, E-cadherin downregulation and cell motility.
This article has been cited by other articles:
|
|
 |
|
  P. Koppikar, V. W. Y. Lui, D. Man, S. Xi, R. L. Chai, E. Nelson, A. B.J. Tobey, and J. R. Grandis Constitutive Activation of Signal Transducer and Activator of Transcription 5 Contributes to Tumor Growth, Epithelial-Mesenchymal Transition, and Resistance to Epidermal Growth Factor Receptor Targeting Clin. Cancer Res., December 1, 2008; 14(23): 7682 - 7690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Kundumani-Sridharan, D. Wang, M. Karpurapu, Z. Liu, C. Zhang, N. Dronadula, and G. N. Rao Suppression of Activation of Signal Transducer and Activator of Transcription-5B Signaling in the Vessel Wall Reduces Balloon Injury-Induced Neointima Formation Am. J. Pathol., October 1, 2007; 171(4): 1381 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Lee, K. Man, R. T.P. Poon, C. M. Lo, A. P. Yuen, I. O. Ng, K. T. Ng, W. Leonard, and S. T. Fan Signal Transducers and Activators of Transcription 5b Activation Enhances Hepatocellular Carcinoma Aggressiveness through Induction of Epithelial-Mesenchymal Transition. Cancer Res., October 15, 2006; 66(20): 9948 - 9956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Akhtar and C. H. Streuli Rac1 links integrin-mediated adhesion to the control of lactational differentiation in mammary epithelia J. Cell Biol., June 5, 2006; 173(5): 781 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Woods, G. Wang, and F. Beier RhoA/ROCK Signaling Regulates Sox9 Expression and Actin Organization during Chondrogenesis J. Biol. Chem., March 25, 2005; 280(12): 11626 - 11634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Clevenger Roles and Regulation of Stat Family Transcription Factors in Human Breast Cancer Am. J. Pathol., November 1, 2004; 165(5): 1449 - 1460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ling and P. E. Lobie RhoA/ROCK Activation by Growth Hormone Abrogates p300/Histone Deacetylase 6 Repression of Stat5-mediated Transcription J. Biol. Chem., July 30, 2004; 279(31): 32737 - 32750. [Abstract] [Full Text] [PDF]
|
|
