MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin

• Published in: Nature (London) Vol. 356; no. 6370; pp. 618 - 622
• Main Authors: Hartwig, J. H, Thelen, M, Resen, A, Janmey, P. A, Nairn, A. C, Aderem, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 16.04.1992; Nature Publishing Group
• Subjects: Actin Cytoskeleton - metabolism; Actin Cytoskeleton - ultrastructure; Actins - metabolism; Actins - ultrastructure; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Binding and carrier proteins; Biological and medical sciences; Brain - metabolism; calcium; Calcium - metabolism; calmodulin; Calmodulin - metabolism; Cattle; Cellular biology; Cross-Linking Reagents; Fundamental and applied biological sciences. Psychology; Homeostasis; Intracellular Signaling Peptides and Proteins; Kinetics; Medical research; Membrane Proteins; Microscopy, Electron; Molecular Sequence Data; Muscles - metabolism; Myristoylated Alanine-Rich C Kinase Substrate; Phosphorylation; protein kinase C; Protein Kinase C - metabolism; Proteins; Proteins - metabolism; Proteins - ultrastructure; Rabbits; Time Factors; Binding protein; Signal transduction; Phosphorylation; Protein kinase C; Regulation(control); Calcium; Enzyme; Actins; Cytoskeleton; Crosslinking; Electron microscopy; Calmodulin
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/356618a0

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.