Phosphorylation of caldesmon by p21-activated kinase. Implications for the Ca2+ sensitivity of smooth muscle contraction

D. Brian Foster, Li Hua Shen, John Kelly, Pierre Thibault, Jennifer Van Eyk, Alan S. Mak

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


We have previously shown that p21-activated kinase, PAK, induces Ca2+- independent contraction of Triton-skinned smooth muscle with concomitant increase in phosphorylation of caldesmon and desmin but not myosin-regulatory light chain (Van Eyk, J. E., Arrell, D. K., Foster, D. B., Strauss, J. D., Heinonen, T. Y., Furmaniak-Kazmierczak, E., Cote, G. P., and Mak, A. S. (1998) J. Biol. Chem. 273, 23433-23439). In this study, we provide biochemical evidence implicating a role for PAK in Ca2+independent contraction of smooth muscle via phosphorylation of caldesmon. Mass spectroscopy data show that stoichiometric phosphorylation occurs at Ser657 and Ser687 abutting the calmodulin-binding sites A and B of chicken gizzard caldesmon, respectively. Phosphorylation of Ser657 and Ser687 has an important functional impact on caldesmon. PAK- phosphorylation reduces binding of caldesmon to calmodulin by about 10-fold whereas binding of calmodulin to caldesmon partially inhibits PAK phosphorylation. Phosphorylated caldesmon displays a modest reduction in affinity for actintropomyosin but is significantly less effective in inhibiting actin-activated S1 ATPase activity in the presence of tropomyosin. We conclude that PAK-phosphorylation of caldesmon at the calmodulin-binding sites modulates caldesmon inhibition of actin-myosin ATPase activity and may, in concert with the actions of Rho-kinase, contribute to the regulation of Ca2+ sensitivity of smooth muscle contraction.

Original languageEnglish (US)
Pages (from-to)1959-1965
Number of pages7
JournalJournal of Biological Chemistry
Issue number3
StatePublished - Jan 21 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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