Mitogen-activated protein kinase activation: An alternate signaling pathway for sustained vascular smooth muscle contraction

Sustained smooth muscle contraction is mediated by protein kinase C (PKC) through a signal transduction cascade leading to contraction. Heat-shock protein 27 (HSP27) appears to be the link between these two major events, i.e., signal transduction and sustained smooth muscle contraction. We have investigated the involvement of HSP27 in signal transduction and HSP27 association with contractile proteins (e.g., actin, myosin, tropomyosin, and caldesmon) resulting in sustained smooth muscle contraction. We have carried out confocal microscopy to investigate the cellular reorganization and colocalization of proteins and immunoprecipitation of HSP27 with actin, myosin, tropomyosin, and caldesmon as detected by sequential immunoblotting. Our results indicate that 1) translocation of Raf-1 to the membrane when stimulated with ceramide is inhibited by vasoactive intestinal peptide (VIP), a relaxant neuropeptide; 2) PKC-α and mitogen-activated protein kinase translocate and colocalize on the membrane in response to ceramide, and PKC-α translocation is inhibited by VIP; 3) HSP27 colocalizes with actin when contraction occurs; and 4) HSP27 immunoprecipitates with actin and with the contractile proteins myosin, tropomyosin, and caldesmon. We propose a model in which HSP27 is involved in sustained smooth muscle contraction and modulates the interaction of actin, myosin, tropomyosin, and caldesmon.

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Characterization of platelet-derived growth factor-induced p38 mitogen-activated protein kinase activation in vascular smooth muscle cells

European Journal of Clinical Investigation ◽

10.1046/j.1365-2362.2001.00865.x ◽

2001 ◽

Vol 31 (8) ◽

pp. 672-680 ◽

Cited By ~ 11

Author(s):

H. Yamaguchi ◽

M. Igarashi ◽

A. Hirata ◽

H. Tsuchiya ◽

S. Susa ◽

...

Keyword(s):

Smooth Muscle ◽

Growth Factor ◽

Protein Kinase ◽

Vascular Smooth Muscle Cells ◽

Mitogen Activated Protein Kinase ◽

Platelet Derived Growth Factor ◽

Kinase Activation ◽

Protein Kinase Activation ◽

Mitogen Activated Protein

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Regulation of vascular smooth muscle contraction: myosin light chain phosphorylation dependent and independent pathways

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y94-200 ◽

1994 ◽

Vol 72 (11) ◽

pp. 1386-1391 ◽

Cited By ~ 33

Author(s):

Yawen Zhang ◽

Suzanne Moreland ◽

Robert S. Moreland

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Muscle Contraction ◽

Light Chain ◽

Myosin Light Chain ◽

Smooth Muscle Contraction ◽

Mitogen Activated Protein ◽

Vascular Smooth Muscle Contraction ◽

Triton X ◽

Mlc Phosphorylation

Ca2+-dependent myosin light chain (MLC) phosphorylation is an important step in the initiation of smooth muscle contraction. However, MLC phosphorylation alone cannot account for all aspects of contractile regulation, suggesting the involvement of other elements. In this article we present evidence obtained from Triton X-100 detergent skinned and intact tissue which demonstrates that vascular smooth muscle contraction can be initiated by a Ca2+-dependent mechanism that does not require prior MLC phosphorylation. We show that Ca2+ can initiate contractions supported by cytidine triphosphate (CTP) and that these contractions are inhibited by calmodulin antagonists, suggesting a Ca2+–calmodulin dependence of force distinct from that for MLC phosphorylation. Evidence is presented to demonstrate that carotid medial fibers contain a mitogen-activated protein (MAP) kinase which is activated by Ca2+ and may catalyze caldesmon phosphorylation. Based in part on our results and those of other investigators, we propose that direct Ca2+–calmodulin binding to caldesmon or phosphorylation of caldesmon by a Ca2+-dependent MAP kinase disinhibits caldesmon. Disinhibition of caldesmon allows an inherent basal level of actin-activated myosin ATPase activity to be expressed. The result is the slow development of force.Key words: mitogen-activated protein kinase, caldesmon, Triton X-100, detergent-skinned fibers, cytidine triphosphate, calmodulin.

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