Differential phosphorylation of LZ+/LZ- MYPT1 isoforms regulates MLC phosphatase activity

Samantha L. Yuen, Ozgur Ogut, Frank V. Brozovich

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The vascular response to NO is due, in part, to a Ca2+ independent activation of myosin light chain (MLC) phosphatase, a trimeric enzyme of 20 kDa, 38 kDa catalytic and 110-130 kDa myosin targeting (MYPT1) subunits. Alternative mRNA splicing produces MYPT1 isoforms that differ by the presence or absence of a central insert (CI) and a leucine zipper (LZ), and the presence of a LZ+ MYPT1 isoform is important for protein kinase G (PKG) mediated activation of MLC phosphatase. This study was designed to determine the molecular basis for the differential sensitivity of the vasculature to NO. Our results demonstrate that the presence of the MYPT1 LZ domain is required for PKG to both phosphorylate MYPT1 at S668 and activate MLC phosphatase. Further for LZ+ MYPT1 isoforms, an S668A MYPT1 mutation prevents the PKG mediated, Ca2+ independent activation of MLC phosphatase. These data demonstrate that differential PKG mediated S668 phosphorylation of LZ+/LZ- MYPT1 isoforms could be important for determining the diversity in the sensitivity of the vasculature to NO mediated vasodilatation. Thus, the relative expression of LZ+/LZ- MYPT1 isoforms, in part, defines the vascular response to NO and NO based vasodilators, and therefore, plays a role in the regulation of vascular tone in both health and disease.

Original languageEnglish (US)
Pages (from-to)37-42
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume562
DOIs
StatePublished - Nov 15 2014

Keywords

  • Nitric oxide
  • Vascular reactivity
  • Vascular tone
  • Vasodilatation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Differential phosphorylation of LZ+/LZ- MYPT1 isoforms regulates MLC phosphatase activity'. Together they form a unique fingerprint.

Cite this