Article reporting that PAK2, a member of the Rho family of GTPase-dependent kinases, regulates isometric tension development and myosin II RLC phosphorylation in saponin permeabilized endothelial monolayers. The results demonstrate that PAK2 can directly phosphorylate MLCK, inhibiting its activity and limiting the development of isometric tension.
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Article reporting that PAK2, a member of the Rho family of GTPase-dependent kinases, regulates isometric tension development and myosin II RLC phosphorylation in saponin permeabilized endothelial monolayers. The results demonstrate that PAK2 can directly phosphorylate MLCK, inhibiting its activity and limiting the development of isometric tension.
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 GTPase-dependent 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 mol 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.
Publication Title:
Journal of Biological Chemistry
Volume:
275
Issue:
24
Page Start:
18366
Page End:
18374
Pages:
9
Peer Reviewed:
Yes
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Goeckeler, Zoe M.; Masaracchia, Ruthann A.; Zeng, Qi; Chew, Teng-Leong; Gallagher, Patricia & Wysolmerski, Robert B.Phosphorylation of Myosin Light Chain Kinase by p21-activated Kinase PAK2,
article,
June 16, 2000;
[Rockville, Maryland].
(https://digital.library.unt.edu/ark:/67531/metadc1871053/:
accessed March 25, 2023),
University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu;
crediting UNT College of Science.
