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Phosphorylation of RhoB by CK1 impedes actin stress fiber organization and epidermal growth factor receptor stabilization

INSERM, U563, CPTP, Département Innovation Thérapeutique et Oncologie Moléculaire, Toulouse F-31052, France.
Experimental Cell Research (Impact Factor: 3.37). 07/2008; 314(15):2811-21. DOI: 10.1016/j.yexcr.2008.06.011
Source: PubMed

ABSTRACT RhoB is a small GTPase implicated in cytoskeletal organization, EGF receptor trafficking and cell transformation. It is an immediate-early gene, regulated at many levels of its biosynthetic pathway. Herein we show that the serine/threonine protein kinase CK1 phosphorylates RhoB in vitro but not RhoA or RhoC. With the use of specific CK1 inhibitors, IC261 and D4476, we show that the kinase phosphorylates also RhoB in HeLa cells. Mass spectrometry analysis demonstrates that RhoB is monophosphorylated by CK1, in its C-terminal end, on serine 185. The substitution of Ser185 by Ala dramatically inhibited the phosphorylation of RhoB in cultured cells. Lastly we show that the inhibition of CK1 activates RhoB and promotes RhoB dependent actin fiber formation and EGF-R level. Our data provide the first demonstration of RhoB phosphorylation and indicate that this post-translational maturation would be a novel critical mechanism to control the RhoB functions.

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    • "properties in pros - tatic cancer ( Hooi et al . , 2006 ; Chen et al . , 2007 ) . Finally , the biological relevance of NAG - 1 in Rho - mediated pathways was fur - ther demonstrated in vivo in a model of tumorigenesis . We and others recently reported direct cross - regulation within the Rho subclass ( Simpson et al . , 2004 ; Ho et al . , 2008 ; Tillement et al . , 2008 ; Steffan et al . , 2009 ) . As a result , the phenotypic modifications in - duced by RhoC silencing in PC - 3 cells might be due to either the repression of RhoC or the concurrent induction of RhoA or RhoB . Of interest , the use of inducible clones over - expressing RhoA recapitulates most of the effects elicited by silencing RhoC , i"
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