A Novel, Multifunctional c-Cbl Binding Protein in Insulin Receptor Signaling in 3T3-L1 Adipocytes

Ribon, Vered; Printen, John A.; Hoffman, Noah G.; Kay, Brian K.; Saltiel, Alan R.

doi:10.1128/mcb.18.2.872

Cited by 208 publications

(231 citation statements)

References 47 publications

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“…Sorbin and SH3 domain-containing 1 (SORBS1) is a human homolog of c-Cbl-associated protein (CAP), 24 which is an important signaling molecule in insulin stimulation of glucose uptake in mouse adipocytes. [24][25][26][27] Phosphorylation of c-Cbl results in the dissociation of the c-Cbl-CAP complex from the insulin receptor and its translocation to a lipid raft domain of the plasma membrane. Subsequent Genetic variants and hypertension Y Yamada et al resistance.…”

Section: Discussionmentioning

confidence: 99%

Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals

Yamada

Ando

Shimokata³

2009

Hypertens Res

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Although various loci and genes have been implicated in predisposition to hypertension by genetic linkage analyses and candidate gene association studies, the genes that confer susceptibility to this condition remain to be identified definitively. We have now examined the relationships of 22 candidate gene polymorphisms with the prevalence of hypertension and with blood pressure (BP) in a 6-year population-based longitudinal cohort study and observed significant relationships of three polymorphisms of SORBS1, GCK and WISP1 with hypertension. The 2233 subjects (1106 women, 1127 men) were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured with subjects having rested in the sitting position for at least 15 min. Genotypes for the 682A-G (Thr228Ala) polymorphism of SORBS1, the À30G-A polymorphism of GCK and the 2364A-G polymorphism of WISP1 were determined by melting curve analysis. Longitudinal analysis with a generalized estimating equation revealed that the polymorphisms of SORBS1 and GCK and that of WISP1 were significantly associated with the prevalence of hypertension in women and men, respectively. Longitudinal analysis with a mixed-effect model revealed that the polymorphism of SORBS1 was significantly related to diastolic BP in women and that those of GCK and WISP1 were significantly related to both systolic and diastolic BP in women and men, respectively. These results suggest that SORBS1 and GCK are susceptibility loci for hypertension in Japanese women and that WISP1 is such a locus in men.

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Section: Discussionmentioning

confidence: 99%

Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals

Yamada

Ando

Shimokata³

2009

Hypertens Res

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“…Interestingly, several Ponsin/SH3P12/CAP mRNA splice variants, are speci®cally up-regulated by p53 expression in EB-1 cells and adriamycin treatment of TK6 cells. In parallel ®ve di erent proteins are recognized with an antibody directed against the carboxy terminal region containing the SH3 domains (Ribon et al, 1998b). It is provocative to imagine that these di erent proteins may have di erent physiological consequences (Mandai et al, 1999).…”

Section: Gip-12mentioning

confidence: 99%

Isolation and characterization of sixteen novel p53 response genes

Kostic

Shaw

2000

Oncogene

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“…This concentration of signaling molecules suggests that these microdomains might function as a site for compartmentalization of signaling events. We observed that insulin stimulated the tyrosine phosphorylation of c-Cbl (14) and its subsequent translocation to a caveolin-enriched, lipid raft membrane fraction (15,16). The c-Cbl-associated protein (CAP)͞Cbl complex interacts with the insulin receptor and dissociates after insulin stimulation, subsequently migrating to rafts because of the interaction of CAP with the lipid raft-associated protein flotillin (17)(18)(19).…”

mentioning

confidence: 94%

The sorbin homology domain: A motif for the targeting of proteins to lipid rafts

Kimura

Baumann

Chiang

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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On phosphorylation of Cbl, the c-Cbl-associated protein (CAP)͞Cbl complex dissociates from the insulin receptor and translocates to a lipid raft membrane fraction to form a ternary complex with flotillin. Deletion analyses of the CAP gene identified a 115-aa region responsible for flotillin binding. This region is homologous to the peptide sorbin and is referred to as the sorbin homology (SoHo) domain. This domain is present in two other proteins, vinexin and ArgBP2. Vinexin also interacted with flotillin, and deletion of its SoHo domain similarly blocked flotillin binding. The overexpression of a CAP mutant in which the SoHo domain had been deleted (CAP⌬SoHo) prevented the translocation of Cbl to lipid rafts and subsequently blocked the recruitment of CrkII and C3G. Moreover, overexpression of CAP⌬SoHo prevented the stimulation of glucose transport and GLUT4 translocation by insulin. These results suggest a mechanism for localization of signaling proteins to the lipid raft that mediates the compartmentalization of crucial signal transduction pathways.L ipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids (1, 2). These regions concentrate certain signaling molecules (3, 4), including heterotrimeric and small G proteins (5-7), Src-family tyrosine kinases (8, 9), endothelial nitric oxide synthase (10, 11), G-proteincoupled receptors (12), and certain tyrosine kinase receptors (13). This concentration of signaling molecules suggests that these microdomains might function as a site for compartmentalization of signaling events. We observed that insulin stimulated the tyrosine phosphorylation of c-Cbl (14) and its subsequent translocation to a caveolin-enriched, lipid raft membrane fraction (15, 16). The c-Cbl-associated protein (CAP)͞Cbl complex interacts with the insulin receptor and dissociates after insulin stimulation, subsequently migrating to rafts because of the interaction of CAP with the lipid raft-associated protein flotillin (17)(18)(19). Moreover, the localization of the Cbl͞CAP complex to this microdomain recruits the guanyl nucleotide exchange protein C3G, resulting in the activation of the G protein TC10. This activation of TC10 generates a PI 3-kinaseindependent signal that is crucial to the regulation of glucose uptake by insulin (20,21).CAP is a multifunctional adapter protein with three SH3 domains in its C terminus and a region of homology to the gut peptide sorbin in its N terminus. The overall sorbin homology (SoHo)͞SH3 organization of CAP is also found in other proteins, including vinexin␣ and ArgBP2A. The similar organization of these proteins suggests that they may similarly function as adapters, linking signaling or cytoskeletal proteins to the lipid raft. We demonstrate here that the SoHo domain does indeed mediate the interaction of CAP and vinexin with flotillin. Moreover, this interaction is crucial for the localization of SH3-binding proteins such as Cbl to the lipid raft and propagation of the downstream signal. These data suggest a signaling par...

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A Novel, Multifunctional c-Cbl Binding Protein in Insulin Receptor Signaling in 3T3-L1 Adipocytes

Cited by 208 publications

References 47 publications

Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals

Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals

Isolation and characterization of sixteen novel p53 response genes

The sorbin homology domain: A motif for the targeting of proteins to lipid rafts

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