Calmodulin and protein kinase C cross-talk: the MARCKS protein is an actin filament and plasma membrane cross-linking protein regulated by protein kinase C phosphorylation and by calmodulin.
The myristoylated, alanine-rich C kinase (PKC) substrate (MARCKS) is a major, specific substrate of PKC that is phosphorylated during macrophage and neutrophil activation, growth factor-dependent mitogenesis and neurosecretion. MARCKS is also a calmodulin-binding protein and binding of calmodulin inhibits phosphorylation of the protein by PKC. Several recent observations from our laboratories suggest a role for MARCKS in cellular morphology and motility. First, in macrophages MARCKS is located at points of cellular adherence where actin filaments insert at the plasma membrane and is released to the cytoplasm upon activation of PKC. Second, during neutrophil chemotaxis MARCKS undergoes a cycle of release from, and reassociation with, the plasma membrane. Third, in vitro, MARCKS is an F-actin cross-linking protein whose activity is inhibited by PKC-mediated phosphorylation and by binding to calmodulin. MARCKS therefore appears to be a regulated cross-bridge between actin and the plasma membrane. Regulation of the plasma membrane-binding and actin-binding properties of MARCKS represents a convergence of the PKC and calmodulin signal transduction pathways in the control of actin cytoskeleton-plasma membrane interactions.
Nairn
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AC
Rockefeller University, New York, NY 10021.
Aderem
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A
D000199:Actins / Q000737:chemistry; D000595:Amino Acid Sequence; D002147:Calmodulin / Q000502:physiology*; D002462:Cell Membrane / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*
D000199:Actins; D002147:Calmodulin; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C