Different molecular mechanisms for Rho family GTPase-dependent, Ca2+- independent contraction of smooth muscle

Jennifer E. Van Eyk, D. Kent Arrell, Darren Brian Foster, John D. Strauss, Taisto Y K Heinonen, Emilia Furmaniak-Kazmierczak, Graham P. Côté, Alan S. Mak

Research output: Contribution to journalArticle

Abstract

Abnormal smooth muscle contraction may contribute to diseases such as asthma and hypertension. Alterations to myosin light chain kinase or phosphatase change the phosphorylation level of the 20-kDa myosin regulatory light chain (MRLC), increasing Ca2+ sensitivity and basal tone. One Rho family GTPase-dependent kinase, Rho-associated kinase (ROK or p160(ROCK)) can induce Ca2+-independent contraction of Triton-skinned smooth muscle by phosphorylating MRLC and/or myosin light chain phosphatase. We show that another Rho family GTPase-dependent kinase, p21-activated protein kinase (PAK), induces Triton-skinned smooth muscle contracts independently of calcium to 62 ± 12% (n = 10) of the value observed in presence of calcium. Remarkably, PAK and ROK use different molecular mechanisms to achieve the Ca2+-independent contraction. Like ROK and myosin light chain kinase, PAK phosphorylates MRLC at serine 19 in vitro. However, PAK-induced contraction correlates with enhanced phosphorylation of caldesmon and desmin but not MRLC. The level of MRLC phosphorylation remains similar to that in relaxed muscle fibers (absence of GST-mPAK3 and calcium) even as the force induced by GST-mPAK3 increases from 26 to 70%. Thus, PAK uncouples force generation from MRLC phosphorylation. These data support a model of PAK-induced contraction in which myosin phosphorylation is at least complemented through regulation of thin filament proteins. Because ROK and PAK homologues are present in smooth muscle, they may work in parallel to regulate smooth muscle contraction.

Original languageEnglish (US)
Pages (from-to)23433-23439
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number36
DOIs
StatePublished - Sep 4 1998
Externally publishedYes

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p21-Activated Kinases
rho GTP-Binding Proteins
GTP Phosphohydrolases
Myosin Light Chains
Protein Kinases
Smooth Muscle
Muscle
Phosphorylation
Myosin-Light-Chain Phosphatase
Myosin-Light-Chain Kinase
Muscle Contraction
Calcium
Phosphotransferases
Smooth Muscle Myosins
Calmodulin-Binding Proteins
rho-Associated Kinases
Desmin
Myosins
Serine
Asthma

ASJC Scopus subject areas

  • Biochemistry

Cite this

Van Eyk, J. E., Kent Arrell, D., Foster, D. B., Strauss, J. D., Heinonen, T. Y. K., Furmaniak-Kazmierczak, E., ... Mak, A. S. (1998). Different molecular mechanisms for Rho family GTPase-dependent, Ca2+- independent contraction of smooth muscle. Journal of Biological Chemistry, 273(36), 23433-23439. https://doi.org/10.1074/jbc.273.36.23433

Different molecular mechanisms for Rho family GTPase-dependent, Ca2+- independent contraction of smooth muscle. / Van Eyk, Jennifer E.; Kent Arrell, D.; Foster, Darren Brian; Strauss, John D.; Heinonen, Taisto Y K; Furmaniak-Kazmierczak, Emilia; Côté, Graham P.; Mak, Alan S.

In: Journal of Biological Chemistry, Vol. 273, No. 36, 04.09.1998, p. 23433-23439.

Research output: Contribution to journalArticle

Van Eyk, JE, Kent Arrell, D, Foster, DB, Strauss, JD, Heinonen, TYK, Furmaniak-Kazmierczak, E, Côté, GP & Mak, AS 1998, 'Different molecular mechanisms for Rho family GTPase-dependent, Ca2+- independent contraction of smooth muscle', Journal of Biological Chemistry, vol. 273, no. 36, pp. 23433-23439. https://doi.org/10.1074/jbc.273.36.23433
Van Eyk, Jennifer E. ; Kent Arrell, D. ; Foster, Darren Brian ; Strauss, John D. ; Heinonen, Taisto Y K ; Furmaniak-Kazmierczak, Emilia ; Côté, Graham P. ; Mak, Alan S. / Different molecular mechanisms for Rho family GTPase-dependent, Ca2+- independent contraction of smooth muscle. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 36. pp. 23433-23439.
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