Cloning and functional characterization of related TC10 isoforms, a subfamily of Rho proteins involved in insulin-stimulated glucose transport

Shian Huey Chiang, June Chunqiu Hou, Joseph Hwang, Jeffrey E. Pessin, Alan R. Saltiel

Research output: Contribution to journalArticle

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Abstract

Insulin stimulates glucose transport via phosphatidylinositol 3-kinase-dependent and -independent pathways. The phosphatidylinositol 3-kinase-independent pathway involves activation of the G protein TC10. A cDNA encoding the mouse homolog of TC10 was cloned, and its gene was mapped at the distal end of chromosome 17. Additionally, a second gene was discovered with ∼70% sequence identity to TC10. We refer to this gene as TC10β. Both isoforms of TC10 were activated by insulin upon transfection in 3T3L1 adipocytes. Cotransfection of cells with TC10α or β plus a dominant negative form of the c-cbl-associated protein CAP prevented the activation by insulin, implicating the CAP/Cbl pathway. Interestingly, both forms of TC10 were also localized in lipid raft fractions in transfected adipocytes. However, although overexpression of TC10α completely blocked glucose transport, TC10β only partially inhibited this process. Furthermore, TC10α overexpression disrupted adipocyte cortical actin, whereas TC10β had little if any effect. Thus, there are two isoforms of this key signaling intermediate, both of which are activated by insulin, but they may play different roles in initiating downstream effectors that influence glucose transport.

Original languageEnglish (US)
Pages (from-to)13067-13073
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number15
DOIs
StatePublished - Apr 12 2002
Externally publishedYes

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Cloning
Organism Cloning
Protein Isoforms
Adipocytes
Phosphatidylinositol 3-Kinase
Insulin
Glucose
Genes
Proteins
Chemical activation
Chromosomes, Human, Pair 17
Chromosomes
GTP-Binding Proteins
Transfection
Actins
Complementary DNA
Lipids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cloning and functional characterization of related TC10 isoforms, a subfamily of Rho proteins involved in insulin-stimulated glucose transport. / Chiang, Shian Huey; Hou, June Chunqiu; Hwang, Joseph; Pessin, Jeffrey E.; Saltiel, Alan R.

In: Journal of Biological Chemistry, Vol. 277, No. 15, 12.04.2002, p. 13067-13073.

Research output: Contribution to journalArticle

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