Smooth muscle myosin phosphatase-associated kinase induces Ca2+ sensitization via myosin phosphatase inhibition.

Journal Article (Journal Article)

Smooth muscle calcium sensitization reflects an inhibition of myosin light chain phosphatase (SMPP-1m) activity; however, the underlying mechanisms are not well understood. SMPP-1m activity can be modulated through phosphorylation of the myosin targeting subunit (MYPT1) by the endogenous myosin phosphatase-associated kinase, MYPT1 kinase (MacDonald, J. A., Borman, M. A., Muranyi, A., Somlyo, A. V., Hartshorne, D. J., and Haystead, T. A. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 2419-2424). Recombinant chicken gizzard MYPT1 (M130) was phosphorylated in vitro by a recombinant MYPT1 kinase, and the sites of phosphorylation were identified as Thr(654), Ser(808), and Thr(675). Introduction of recombinant MYPT1 kinase elicited a calcium-independent contraction in beta-escin-permeabilized rabbit ileal smooth muscle. Using an antibody that specifically recognizes MYPT1 phosphorylated at Thr(654) (M130 numbering), we determined that this calcium-independent contraction was correlated with an increase in MYPT1 phosphorylation. These results indicate that SMPP-1m phosphorylation by MYPT1 kinase is a mechanism of smooth muscle calcium sensitization.

Full Text

Duke Authors

Cited Authors

  • Borman, MA; MacDonald, JA; Murányi, A; Hartshorne, DJ; Haystead, TAJ

Published Date

  • June 28, 2002

Published In

Volume / Issue

  • 277 / 26

Start / End Page

  • 23441 - 23446

PubMed ID

  • 11976330

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M201597200


  • eng

Conference Location

  • United States