Loading…

Site-specific Phosphorylation and Point Mutations of Telokin Modulate Its Ca2+-desensitizing Effect in Smooth Muscle

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) mutant...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2001-07, Vol.276 (27), p.24519-24524
Main Authors: Walker, L A, MacDonald, J A, Liu, X, Nakamoto, R K, Haystead, T A, Somlyo, A V, Somlyo, A P
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 Ca 2+ -desensitizing effect of telokin on force.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M103560200