title: MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin.
abstract: AGONISTS that stimulate protein kinase C (PKC) induce profound changes in cell morphology correlating with the reorganization of submembranous actin, but no direct connection between PKC and actin assembly has been identified. The myristoylated, alanine-rich C kinase substrate (MARCKS) binds calmodulin and is a predominant, specific substrate of PKC which is phosphorylated during macrophage and neutrophil activation , growth factor-dependent mitogenesis and neurosecretion; it is redistributed from plasma membrane to cytoplasm when phosphorylated and is involved in leukocyte motility. Here we report that MARCKS is a filamentous (F) actin crosslinking protein, with activity that is inhibited by PKC-mediated phosphorylation and by binding to calcium-calmodulin. MARCKS may be a regulated crossbridge between actin and the plasma membrane, and modulation of the actin crosslinking activity of the MARCKS protein by calmodulin and phosphorylation represents a potential convergence of the calcium-calmodulin and PKC signal transduction pathways in the regulation of the actin cytoskeleton.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: J H
authors.initials: JH
authors.lastname: Hartwig
authors.forename: M
authors.initials: M
authors.lastname: Thelen
authors.forename: A
authors.initials: A
authors.lastname: Rosen
authors.forename: P A
authors.initials: PA
authors.lastname: Janmey
authors.forename: A C
authors.initials: AC
authors.lastname: Nairn
authors.forename: A
authors.initials: A
authors.lastname: Aderem
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002417:Cattle; D003432:Cross-Linking Reagents; D006706:Homeostasis; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008565:Membrane Proteins; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism* / Q000648:ultrastructure; D011817:Rabbits; D013997:Time Factors
chemical_list: D000199:Actins; D002147:Calmodulin; D003432:Cross-Linking Reagents; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C; D002118:Calcium