Okadaic acid-sensitive protein phosphatases dephosphorylate MARCKS, a major protein kinase C substrate

FEBS Lett. 1993 Dec 20;336(1):37-42. doi: 10.1016/0014-5793(93)81604-x.

Abstract

The myristoylated alanine-rich C kinase substrate (MARCKS) undergoes a rapid and, in certain circumstances, transient increase in phosphorylation in response to stimuli that activate protein kinase C. We have investigated the protein-serine/threonine phosphatase activity responsible for reversing the phosphorylation of MARCKS. In cell-free assays, protein phosphatases 1, 2A and 2C (PP1, PP2A and PP2C) all dephosphorylate recombinant MARCKS or a synthetic peptide based on its phosphorylation site domain. In intact Swiss 3T3 cells, okadaic acid, a specific inhibitor of PP1 and PP2A, had little effect on MARCKS phosphorylation on its own, but largely prevented the dephosphorylation of MARCKS that occurred following activation of protein kinase C by bombesin with subsequent receptor blockade. These results indicate that although the dephosphorylation of MARCKS can be mediated by PP2C in vitro, this protein is dephosphorylated by okadaic acid-sensitive phosphatases in the intact cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Catalysis
  • Ethers, Cyclic / pharmacology*
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Proteins*
  • Mice
  • Molecular Sequence Data
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Okadaic Acid
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation / drug effects
  • Protein Kinase C / metabolism*
  • Proteins / metabolism*
  • Substrate Specificity

Substances

  • Ethers, Cyclic
  • Intracellular Signaling Peptides and Proteins
  • Marcks protein, mouse
  • Membrane Proteins
  • Proteins
  • Myristoylated Alanine-Rich C Kinase Substrate
  • Okadaic Acid
  • Protein Kinase C
  • Phosphoprotein Phosphatases