Site-specific phosphorylation and point mutations of telokin modulate its Ca2+-desensitizing effect in smooth muscle.

Journal Article

Forskolin and 8-bromoguanosine 3'-5'-cyclic monophosphate (8-Br-cGMP) induce phosphorylation of Ser-13 of telokin and relaxation of smooth muscle at constant calcium. Comparison with the effect of wild type with aspartate (D; to mimic phosphorylation) and alanine (A; non-phosphorylatable) mutants of telokin showed that the S13D mutant was more effective than wild type in relaxing smooth muscle at constant calcium. The efficacy of the Ser-13A, S12A, and S12D mutants was not significantly different from that of wild-type telokin. The effect of neither S13D nor Ser-13A was affected by 8-Br-cGMP, whereas the effect of wild type, S12A, and S12D was enhanced by 8-Br-cGMP, indicating the specificity of Ser-13 charge modification. Mutation of Ser-19 (a mitogen-activated protein kinase site) showed the S19A to be more effective than, and S19D to be not different from, wild-type telokin. The effect of both mutants was slightly enhanced by 8-Br-cGMP. A truncated (residues 1-142) form lacking the acidic C terminus had the same relaxant effect as wild-type telokin, whereas the C-terminal peptide (residues 142-155) had no effect. We conclude that site-specific modification of the N terminus modulates the Ca2+ -desensitizing effect of telokin on force.

Full Text

Duke Authors

Cited Authors

  • Walker, LA; MacDonald, JA; Liu, X; Nakamoto, RK; Haystead, TA; Somlyo, AV; Somlyo, AP

Published Date

  • July 6, 2001

Published In

Volume / Issue

  • 276 / 27

Start / End Page

  • 24519 - 24524

PubMed ID

  • 11346659

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M103560200

Language

  • eng

Conference Location

  • United States