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

Nature. 1992 Apr 16;356(6370):618-22. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / ultrastructure*
  • Actins / metabolism*
  • Actins / ultrastructure
  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • Calcium / metabolism*
  • Calmodulin / metabolism*
  • Cattle
  • Cross-Linking Reagents
  • Homeostasis
  • Intracellular Signaling Peptides and Proteins*
  • Kinetics
  • Membrane Proteins*
  • Microscopy, Electron
  • Molecular Sequence Data
  • Muscles / metabolism*
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Proteins / metabolism*
  • Proteins / ultrastructure
  • Rabbits
  • Time Factors


  • Actins
  • Calmodulin
  • Cross-Linking Reagents
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Proteins
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Protein Kinase C
  • Calcium