This is an archive of papers published by the staff and faculty of Fox Chase Cancer Center. For questions about content, please contact Talbot Research Library
Last updated on
Bagrodia S , Taylor SJ , Creasy CL , Chernoff J , Cerione RA
Identification of a Mouse P21(Cdc42/Rac) Activated Kinase
Journal of Biological Chemistry. 1995 Sep 29;270(39) :22731-22737
AbstractWe have isolated a novel member of the mammalian PAI( (p21 activated kinase) and yeast Ste20 serine/threonine kinase family from a mouse fibroblast cDNA library, designated mPAK-3. Expression of mPAK-3 in Saccharomyces cerevisiae partially restores mating function in ste20 null cells. Like other PAKs, mPAK-3 contains a putative Cdc42Hs/Rac binding sequence and when transiently expressed in COS cells, full-length mPAK-3 binds activated (GTP gamma S (guanosine 5'-3-O- (thiotriphosphate)-bound) glutathione S-transferase (GST)- Cdc42Hs and GST-Rac1 but not GST-RhoA. As expected for a putative target molecule, mPAX-3 does not bind to an effector domain mutant of Cdc42Hs. Furthermore, activated His-tagged Cdc42Hs and His-tagged Rac stimulate mPAK-3 autophosphorylation and phosphorylation of myelin basic protein by mPAK-3 in vitro. Interestingly, the amino-terminal region of mPAK-3 contains potential SH3-binding sites and we find that mPAK-3, expressed in vitro and in vivo, shows highly specific binding to the SH3 domain of phospholipase C-gamma and at least one SH3 domain in the adapter protein Nck. These results raise the possibility of an additional level of regulation of the PAK family in vivo.
NotesTimes Cited: 209 Article RY054 J BIOL CHEM