Regulation of Phospholipase C-δ1 through Direct Interactions with the Small GTPase Ral and Calmodulin*

  1. Rajinder P. Bhullar
  1. Departments of Oral Biology and Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba R3E 0W2, Canada
  1. To whom correspondence should be addressed: Dept. of Oral Biology, Faculty of Dentistry, University of Manitoba, Winnipeg, MB R3E 0W2, Canada. Tel.: 204-789-3703; Fax: 204-789-3713; E-mail: bhullar{at}MS.Umanitoba.CA.

Abstract

Second messengers generated from membrane lipids play a critical role in signaling and control diverse cellular processes. Despite being one of the most evolutionarily conserved of all the phosphoinositide-specific phospholipase C (PLC) isoforms, a family of enzymes responsible for hydrolysis of the membrane lipid phosphatidylinositol bisphosphate, the mechanism of PLC-δ1 activation is still poorly understood. Here we report a novel regulatory mechanism for PLC-δ1 activation that involves direct interaction of the small GTPase Ral and the universal calcium-signaling molecule calmodulin (CaM) with PLC-δ1. In addition, we have identified a novel IQ type CaM binding motif within the catalytic region of PLC-δ1 that is not found in other PLC isoforms. Binding of CaM at the IQ motif inhibits PLC-δ1 activity, while addition of Ral reverses the inhibition. The overexpression of various Ral mutants in cells potentiates PLC-δ1 activity. Thus, the Ral-CaM complex defines a multifaceted regulatory mechanism for PLC-δ1 activation.

  • Received November 16, 2004.
  • Revision received April 1, 2005.
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This Article

  1. The Journal of Biological Chemistry 280, 21933-21941.
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