title: Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes.
abstract: Osmotic shock induces GLUT4 translocation and glucose uptake through a mechanism independent of PI 3-kinase, but dependent on tyrosine phosphorylation of cellular proteins. To identify the tyrosine phosphorylated proteins required for osmotic shock-stimulated glucose uptake, we examined tyrosine phosphorylation of candidate proteins, and found that the 60-80kDa species including paxillin and the 120-130kDa species including p130Cas, PYK2, FAK and Gab1 were tyrosine-phosphorylated in response to osmotic shock. Inhibition of actin polymerization by cytochalasin D significantly decreased the tyrosine phosphorylation of paxillin, p130Cas, PYK2 and FAK but not Gab1, but had no effect on 2-deoxyglucose (DOG) uptake, suggesting a role for Gab1 in osmotic shock-induced glucose transport. Also, we found that osmotic shock increases the association of phospholipase C-gamma (PLC-gamma) with Gab1 and stimulates tyrosine phosphorylation of PLC-gamma itself. The PLC inhibitor, U73122, inhibited osmotic shock-induced 2-DOG uptake. These results suggest that tyrosine phosphorylation of Gab1 and subsequent recruitment and activation of PLC-gamma may play a role in osmotic shock-induced glucose transport.
authors.affiliation: First Department of Medicine, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Ueno
authors.forename: T
authors.initials: T
authors.lastname: Haruta
authors.forename: T
authors.initials: T
authors.lastname: Uno
authors.forename: I
authors.initials: I
authors.lastname: Usui
authors.forename: M
authors.initials: M
authors.lastname: Iwata
authors.forename: A
authors.initials: A
authors.lastname: Takano
authors.forename: J
authors.initials: J
authors.lastname: Kawahara
authors.forename: T
authors.initials: T
authors.lastname: Sasaoka
authors.forename: O
authors.initials: O
authors.lastname: Ishibashi
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015638:Cytochalasin D / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015151:Immunoblotting; D007527:Isoenzymes / Q000502:physiology*; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009997:Osmotic Pressure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D011233:Precipitin Tests; D010738:Type C Phospholipases / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015638:Cytochalasin D; D003847:Deoxyglucose; D005947:Glucose; D007527:Isoenzymes; D019384:Nucleic Acid Synthesis Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D051966:Phospholipase C gamma; D010750:Phosphoproteins; D010738:Type C Phospholipases; D014443:Tyrosine; C490897:Gab1 protein, mouse