Tyrosine phosphorylation of Munc18c regulates platelet-derived growth factor-stimulated glucose transporter 4 translocation in 3T3L1 adipocytes

Mitsuhiko Umahara, Shuichi Okada, Eijiro Yamada, Tsugumichi Saito, Kihachi Ohshima, Koshi Hashimoto, Masanobu Yamada, Hiroyuki Shimizu, Jeffrey E. Pessin, Masatomo Mori

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Abstract

Platelet-derived growth factor (PDGF) stimulation of skeletal muscle, cultured myotubes, and 3T3L1 adipocytes results in glucose transporter 4 (Glut4) translocation, albeit to a reduced level compared with insulin. To address the mechanism of PDGF action, we have determined that the Syntaxin 4 negative regulatory protein, Munc18c, undergoes PDGF-stimulated phosphorylation on tyrosine residue 521. The tyrosine phosphorylation of Munc18c on Y521 occurred concomitant with the dissociation of the Munc18c protein from Syntaxin 4 in a time frame consistent with Glut4 translocation. Moreover, expression of the wild-type Munc18c protein did not inhibit PDGF-induced Glut4 translocation, whereas expression of Y521A-Munc18c mutant was inhibitory and failed to dissociate from Syntaxin 4. In contrast, expression of either wild-type Munc18c or the Y521A-Munc18c mutant both resulted in a marked inhibition of insulin-stimulated Glut4 translocation. Together, these data demonstrate that one mechanism accounting for the PDGF induction of Glut4 translocation is the suppression of the Munc18c negative regulation of Syntaxin 4 function.

Original languageEnglish (US)
Pages (from-to)40-49
Number of pages10
JournalEndocrinology
Volume149
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

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Facilitative Glucose Transport Proteins
Platelet-Derived Growth Factor
Qa-SNARE Proteins
Munc18 Proteins
Adipocytes
Tyrosine
Phosphorylation
Insulin
Skeletal Muscle Fibers
Skeletal Muscle

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Tyrosine phosphorylation of Munc18c regulates platelet-derived growth factor-stimulated glucose transporter 4 translocation in 3T3L1 adipocytes. / Umahara, Mitsuhiko; Okada, Shuichi; Yamada, Eijiro; Saito, Tsugumichi; Ohshima, Kihachi; Hashimoto, Koshi; Yamada, Masanobu; Shimizu, Hiroyuki; Pessin, Jeffrey E.; Mori, Masatomo.

In: Endocrinology, Vol. 149, No. 1, 01.2008, p. 40-49.

Research output: Contribution to journalArticle

Umahara, M, Okada, S, Yamada, E, Saito, T, Ohshima, K, Hashimoto, K, Yamada, M, Shimizu, H, Pessin, JE & Mori, M 2008, 'Tyrosine phosphorylation of Munc18c regulates platelet-derived growth factor-stimulated glucose transporter 4 translocation in 3T3L1 adipocytes', Endocrinology, vol. 149, no. 1, pp. 40-49. https://doi.org/10.1210/en.2006-1549
Umahara, Mitsuhiko ; Okada, Shuichi ; Yamada, Eijiro ; Saito, Tsugumichi ; Ohshima, Kihachi ; Hashimoto, Koshi ; Yamada, Masanobu ; Shimizu, Hiroyuki ; Pessin, Jeffrey E. ; Mori, Masatomo. / Tyrosine phosphorylation of Munc18c regulates platelet-derived growth factor-stimulated glucose transporter 4 translocation in 3T3L1 adipocytes. In: Endocrinology. 2008 ; Vol. 149, No. 1. pp. 40-49.
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