What question did this study set out to answer?

To determine the role of Cbl and its pYXXM motifs in activating phosphatidylinositol 3-kinase, atypical protein kinase C, and glucose transport during insulin signaling in adipocytes.

November 12, 2004Biochemistry

Requirements for pYXXM Motifs in Cbl for Binding to the p85 Subunit of Phosphatidylinositol 3-Kinase and Crk, and Activation of Atypical Protein Kinase C and Glucose Transport during Insulin Action in 3T3/L1 Adipocytes

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Authors

MSMary L. StandaertJoslin Diabetes Center MSMini P. SajanUnited States Department of Veterans Affairs AMAtsushi MiuraNihon University

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Implication

Experimental study reveals that Cbl pYXXM motifs regulate kinase activation and Glut4 translocation in adipocytes, indicating dual pathways coordinate insulin-stimulated glucose uptake.

Key Points

To determine the role of Cbl and its pYXXM motifs in activating phosphatidylinositol 3-kinase, atypical protein kinase C, and glucose transport during insulin signaling in adipocytes.
Expressed Y371F and Y731F Cbl mutants in 3T3/L1 adipocytes to abolish pYXXM-mediated binding to SH2 domains of downstream targets.
Measured Crk and p85 binding, atypical protein kinase C activation and membrane translocation, Glut4 translocation, and glucose transport, with wild-type Cbl coexpression testing rescue.
Cbl mutants suppressed insulin-stimulated binding to Crk and the p85 subunit of PI 3-kinase, while inhibiting atypical protein kinase C activation and membrane translocation.
Mutant expression markedly decreased Glut4 translocation and glucose transport, which were successfully rescued by wild-type Cbl coexpression.
Cbl mutants selectively impaired Cbl-dependent PI 3-kinase activity without significantly inhibiting IRS-1-mediated PI 3-kinase activation.

Cite This Study

Standaert et al. (2004) studied this question.

synapsesocial.com/papers/6a9d5aaad8a02169be46dbed https://doi.org/10.1021/bi049222q

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Implication

Experimental study reveals that Cbl pYXXM motifs regulate kinase activation and Glut4 translocation in adipocytes, indicating dual pathways coordinate insulin-stimulated glucose uptake.

Requirements for pYXXM Motifs in Cbl for Binding to the p85 Subunit of Phosphatidylinositol 3-Kinase and Crk, and Activation of Atypical Protein Kinase C and Glucose Transport during Insulin Action in 3T3/L1 Adipocytes

Discussion

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Implication

Key Points

Cite This Study

Requirements for pYXXM Motifs in Cbl for Binding to the p85 Subunit of Phosphatidylinositol 3-Kinase and Crk, and Activation of Atypical Protein Kinase C and Glucose Transport during Insulin Action in 3T3/L1 Adipocytes

Discussion

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Key Points

Cite This Study

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