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Modulation of smooth muscle contractility by CHASM, a novel member of the smoothelin family of proteins
Author(s) -
Borman Meredith A.,
MacDonald Justin A.,
Haystead Timothy A.J.
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.08.002
Subject(s) - calponin , actin , microbiology and biotechnology , biology , kinase , calmodulin , chemistry , biochemistry , enzyme
Cyclic nucleotides acting through their associated protein kinases, the cGMP‐ and cAMP‐dependent protein kinases, can relax smooth muscles without a change in free intracellular calcium concentration ([Ca 2+ ] i ), a phenomenon referred to as Ca 2+ desensitization. The molecular mechanisms by which these kinases bring about Ca 2+ desensitization are unknown and an understanding of this phenomenon may lead to better therapies for treating diseases involving defects in the contractile response of smooth muscles such as hypertension, bronchospasm, sexual dysfunction, gastrointestinal disorders and glaucoma. Utilizing a combination of real‐time proteomics and smooth muscle physiology, we characterized a distinct subset of protein targets for cGMP‐dependent protein kinase in smooth muscle. Among those phosphoproteins identified was calponin homology‐associated smooth muscle (CHASM), a novel protein that contains a calponin homology domain and shares sequence similarity with the smoothelin family of smooth muscle specific proteins. Recombinant CHASM was found to evoke relaxation in a concentration dependent manner when added to permeabilized smooth muscle. A co‐sedimentation assay with actin demonstrated that CHASM does not possess actin binding activity. Our findings indicate that CHASM is a novel member of the smoothelin protein family that elicits Ca 2+ desensitization in smooth muscle.