Regulation of phospholipase C-delta1 through direct interactions with the small GTPase Ral and calmodulin.
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-delta1 ... activation is still poorly understood. Here we report a novel regulatory mechanism for PLC-delta1 activation that involves direct interaction of the small GTPase Ral and the universal calcium-signaling molecule calmodulin (CaM) with PLC-delta1. In addition, we have identified a novel IQ type CaM binding motif within the catalytic region of PLC-delta1 that is not found in other PLC isoforms. Binding of CaM at the IQ motif inhibits PLC-delta1 activity, while addition of Ral reverses the inhibition. The overexpression of various Ral mutants in cells potentiates PLC-delta1 activity. Thus, the Ral-CaM complex defines a multifaceted regulatory mechanism for PLC-delta1 activation.
Mesh Terms:
Amino Acid Motifs, Animals, Blotting, Western, Calcium, Calmodulin, Catalysis, Catalytic Domain, Cattle, Cell Membrane, Cytosol, DNA, Complementary, Escherichia coli, GTP Phosphohydrolases, Gene Library, Glutathione Transferase, HeLa Cells, Humans, Hydrolysis, Isoenzymes, Models, Molecular, Mutation, Peptides, Phosphates, Phosphatidylinositols, Phospholipase C delta, Plasmids, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Rats, Recombinant Fusion Proteins, Recombinant Proteins, Signal Transduction, Temperature, Transfection, Two-Hybrid System Techniques, Type C Phospholipases, ral GTP-Binding Proteins
Amino Acid Motifs, Animals, Blotting, Western, Calcium, Calmodulin, Catalysis, Catalytic Domain, Cattle, Cell Membrane, Cytosol, DNA, Complementary, Escherichia coli, GTP Phosphohydrolases, Gene Library, Glutathione Transferase, HeLa Cells, Humans, Hydrolysis, Isoenzymes, Models, Molecular, Mutation, Peptides, Phosphates, Phosphatidylinositols, Phospholipase C delta, Plasmids, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Rats, Recombinant Fusion Proteins, Recombinant Proteins, Signal Transduction, Temperature, Transfection, Two-Hybrid System Techniques, Type C Phospholipases, ral GTP-Binding Proteins
J. Biol. Chem.
Date: Jun. 10, 2005
PubMed ID: 15817490
View in: Pubmed Google Scholar
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