Membrane Environment Exerts an Important Influence on Rac-Mediated Activation of Phospholipase C gamma 2

We performed analyses of the molecular mechanisms involved in the regulation of phospholipase C gamma 2 (PLC gamma 2). We identified several regions in the PLC gamma -specific array, gamma SA, that contribute to autoinhibition in the basal state by occlusion of the catalytic domain. While the activa...

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Published inMolecular and cellular biology Vol. 31; no. 6; pp. 1240 - 1251
Main Authors Everett, Katy L, Buehler, Anja, Bunney, Tom D, Margineanu, Anca, Baxendale, Rhona W, Vatter, Petra, Retlich, Michael, Walliser, Claudia, Manning, Hugh B, Neil, Mark AA, Dunsby, Christopher, French, Paul MW, Gierschik, Peter, Katan, Matilda
Format Journal Article
LanguageEnglish
Published 15.03.2011
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Summary:We performed analyses of the molecular mechanisms involved in the regulation of phospholipase C gamma 2 (PLC gamma 2). We identified several regions in the PLC gamma -specific array, gamma SA, that contribute to autoinhibition in the basal state by occlusion of the catalytic domain. While the activation of PLC gamma 2 by Rac2 requires stable translocation to the membrane, the removal of the domains required for membrane translocation in the context of an enzyme with impaired autoinhibition generated constitutive, highly active PLC in cells. We further tested the possibility that the interaction of PLC gamma 2 with its activator protein Rac2 was sufficient for activation through the release of autoinhibition. However, we found that Rac2 binding in the absence of lipid surfaces was not able to activate PLC gamma 2. Together with other observations, these data suggest that an important consequence of Rac2 binding and translocation to the membrane is that membrane proximity, on its own or together with Rac2, has a role in the release of autoinhibition, resulting in interfacial activation.
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ISSN:0270-7306
DOI:10.1128/MCB.01408-10