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001-es BibID:	BIBFORM058126
Első szerző:	Brodie, Chaya
Cím:	PKCdelta associates with and is involved in the phosphorylation of RasGRP3 in response to phorbol esters / Chaya Brodie, Rivka Steinhart, Gila Kazimirsky, Hadara Rubinfeld, Tehila Hyman, Jolene N. Ayres, Gang Min Hur, Attila Toth, Dazhi Yang, Susan H. Garfield, James C. Stone, Peter M. Blumberg
Dátum:	2004
ISSN:	0026-895X
Megjegyzések:	RasGRP is a family of guanine nucleotide exchange factors that activate small GTPases and contain a C1 domain similar to the one present in protein kinase C (PKC). In this study, we examined the interaction of RasGRP3 and PKC in response to the phorbol ester PMA. In Chinese hamster ovary or LN-229 cells heterologously expressing RasGRP3, phorbol 12-myristate 13-acetate (PMA) induced translocation of RasGRP3 to the perinuclear region and a decrease in the electrophoretic mobility of RasGRP3. The mobility shift was associated with phosphorylation of RasGRP3 on serine residues and seemed to be PKCdelta-dependent because it was blocked by the PKCdelta inhibitor rottlerin as well as by a PKCdelta kinase-dead mutant. Using coimmunoprecipitation, we found that PMA induced the physical association of RasGRP3 with PKCdelta and, using in situ methods, we showed colocalization of PKCdelta and RasGRP3 in the perinuclear region. PKCdelta phosphorylated RasGRP3 in vitro. Previous studies suggest that ectopic expression of RasGRP3 increases activation of Erk1/2. We found that overexpression of either PKCdelta or RasGRP3 increased the activation of Erk1/2 by PMA. In contrast, coexpression of PKCdelta and RasGRP3 yielded a level of phosphorylation of Erk1/2 similar to that of control vector cells. Our results suggest that PKCdelta may act as an upstream kinase associating with and phosphorylating RasGRP3 in response to PMA. The interaction between RasGRP3 and PKCdelta points to the existence of complex cross-talk between various members of the phorbol ester receptors which can have important impact on major signal transduction pathways and cellular processes induced by phorbol esters or DAG
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Molecular Pharmacology. - 66 : 1 (2004), p. 76-84. -
További szerzők:	Steinhart, Rivka Kazimirsky, Gila Rubinfeld, Hadara Hyman, Tehila Ayres, Jolene N. Min Hur, Gang Tóth Attila (1971-) (biológus) Yang, Dazhi Garfield, Susan H. Stone, James C. Blumberg, Peter M.
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