Agonist-induced force enhancement: The role of isoforms and phosphorylation of the myosin-targeting subunit of myosin light chain phosphatase

Christopher T. Richards, Ozgur Ogut, Frank V. Brozovich

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The magnitude of agonist-induced Ca2+ sensitization of force is tissue-dependent, but an explanation for this diversity is unknown. Ca2+ sensitization is thought to involve a G-protein-mediated inhibition of myosin light chain phosphatase activity by phosphorylation of the myosin-targeting subunit (MYPT). The MYPT has two isoforms that differ by a central insert, which lies near this phosphorylation site. Expression of MYPT isoforms is both developmentally regulated and tissue-specific. We hypothesized that the presence or absence of the central insert determines the magnitude of agonist-induced Ca2+ sensitization. Throughout development, the chicken aorta exclusively expresses the splice-in MYPT isoform, and guanosine 5′-O-(thiotriphosphate) (GTPγS) produces a significant force enhancement. Early during development, the chicken gizzard expresses the splice-in MYPT isoform, and GTPγS produced a Ca2+ sensitization. In the gizzard coincident with the shift in expression from the splice-in to splice-out MYPT isoform, GTPγS no longer produced force enhancement. In addition, adenosine 5′-O-(thiotriphosphate) (ATPγS) phosphorylated only adult gizzard tissue, the only tissue that did not demonstrate a Ca2+ sensitization. These results suggest that the relative expression of splice-in/splice-out MYPT isoforms determines the magnitude of agonist-induced force enhancement and that MYPT phosphorylation is not required for Ca2+ sensitization.

Original languageEnglish (US)
Pages (from-to)4422-4427
Number of pages6
JournalJournal of Biological Chemistry
Volume277
Issue number6
DOIs
StatePublished - Feb 8 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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