Phosphorylation of myosin light chain kinase by p21-activated kinase PAK2

Zoe M. Goeckeler, Ruthann A. Masaracchia, Qi Zeng, Teng Leong Chew, Patricia Gallagher, Robert B. Wysolmerski

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Phosphorylation of myosin II regulatory light chains (RLC) by Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) is a critical step in the initiation of smooth muscle and non-muscle cell contraction. Post-translational modifications to MLCK down-regulate enzyme activity, suppressing RLC phosphorylation, myosin II activation, and tension development. Here we report that PAK2, a member of the Rho family of GTPasedependent kinases, regulates isometric tension development and myosin II RLC phosphorylation in saponin permeabilized endothelial monolayers. PAK2 blunts tension development by 75% while inhibiting diphosphorylation of myosin II RLC. Cdc42-activated placenta and recombinant, constitutively active PAK2 phosphorylate MLCK in vitro with a stoichiometry of 1.71 ± 0.21 tool of PO4/mol of MLCK. This phosphorylation inhibits MLCK phosphorylation of myosin II RLC. PAK2 catalyzes MLCK phosphorylation on serine residues 439 and 991. Binding calmodulin to MLCK blocks phosphorylation of Ser-991 by PAK2. These results demonstrate that PAK2 can directly phosphorylate MLCK, inhibiting its activity and limiting the development of isometric tension.

Original languageEnglish (US)
Pages (from-to)18366-18374
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number24
DOIs
StatePublished - Jun 16 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Goeckeler, Z. M., Masaracchia, R. A., Zeng, Q., Chew, T. L., Gallagher, P., & Wysolmerski, R. B. (2000). Phosphorylation of myosin light chain kinase by p21-activated kinase PAK2. Journal of Biological Chemistry, 275(24), 18366-18374. https://doi.org/10.1074/jbc.M001339200