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

Endocrinology. 2008 Jan;149(1):40-9. doi: 10.1210/en.2006-1549. Epub 2007 Oct 4.


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.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Adipocytes / physiology
  • Animals
  • Catalytic Domain / drug effects
  • Catalytic Domain / physiology
  • Cell Differentiation / drug effects
  • Glucose Transporter Type 4 / metabolism*
  • Insulin / pharmacology
  • Mice
  • Munc18 Proteins / metabolism*
  • Munc18 Proteins / physiology*
  • Phosphorylation
  • Platelet-Derived Growth Factor / pharmacology*
  • Protein Binding / drug effects
  • Protein Transport / drug effects
  • Protein-Tyrosine Kinases / metabolism*
  • Qa-SNARE Proteins / metabolism
  • Qa-SNARE Proteins / physiology
  • Tyrosine / metabolism


  • Glucose Transporter Type 4
  • Insulin
  • Munc18 Proteins
  • Platelet-Derived Growth Factor
  • Qa-SNARE Proteins
  • Slc2a4 protein, mouse
  • Tyrosine
  • Protein-Tyrosine Kinases