PYK2 as a mediator of endothelin-1/G alpha 11 signaling to GLUT4 glucose transporters
UMass Chan Affiliations
Program in Molecular Medicine and Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2001-10-17Keywords
3T3 CellsAnimals
Endothelin-1
Focal Adhesion Kinase 2
GTP-Binding Protein alpha Subunits, Gq-G11
Glucose Transporter Type 4
Heterotrimeric GTP-Binding Proteins
Mice
Microscopy, Fluorescence
Monosaccharide Transport Proteins
*Muscle Proteins
Protein Transport
Protein-Tyrosine Kinases
Signal Transduction
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Endothelin-1 (ET-1) signaling through G alpha(q/11) stimulates translocation of intracellular GLUT4 glucose transporters to the plasma membrane of 3T3-L1 adipocytes by an unknown mechanism that requires protein tyrosine phosphorylation and ADP-ribosylation factor 6 (ARF6) but is independent of phosphatidylinositol 3 (PI3)-kinase. In contrast, insulin action on this process requires PI3-kinase but not ARF6. Here we report the identification of two proteins selectively tyrosine-phosphorylated in response to ET-1 but not insulin: the Ca(2+)-activated tyrosine kinase PYK2 and its physiological substrate, the adhesion scaffold protein paxillin. Endogenous paxillin as well as expressed Myc-tagged PYK2 or a Myc-tagged kinase-deficient PYK2 protein were acutely directed to F-actin-rich adhesion sites from the adipocyte cytoplasm in response to ET-1 but not insulin. CADTK-related non-kinase (CRNK) is a dominant negative form of PYK2 containing the C-terminal portion of the protein, which binds paxillin but lacks the PYK2 autophosphorylation site (Tyr(402)). CRNK expression in 3T3-L1 adipocytes inhibited ET-1-mediated F-actin polymerization and translocation of Myc-tagged GLUT4-enhanced green fluorescent protein (EGFP) to the plasma membrane without disrupting insulin action on these processes. These data reveal the tyrosine kinase PYK2 as a required signaling element in the regulation of GLUT4 recycling in 3T3-L1 adipocytes by ET-1, whereas insulin signaling is directed through a different pathway.Source
J Biol Chem. 2001 Dec 21;276(51):47751-4. Epub 2001 Oct 15. Link to article on publisher's siteDOI
10.1074/jbc.C100524200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/42380PubMed ID
11602570Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.C100524200
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