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CIN85 modulates TGF? signaling by promoting the presentation of TGF? receptors on the cell surface.

ABSTRACT: Members of the transforming growth factor ? (TGF?) family initiate cellular responses by binding to TGF? receptor type II (T?RII) and type I (T?RI) serine/threonine kinases, whereby Smad2 and Smad3 are phosphorylated and activated, promoting their association with Smad4. We report here that T?RI interacts with the SH3 domains of the adaptor protein CIN85 in response to TGF? stimulation in a TRAF6-dependent manner. Small interfering RNA-mediated knockdown of CIN85 resulted in accumulation of T?RI in intracellular compartments and diminished TGF?-stimulated Smad2 phosphorylation. Overexpression of CIN85 instead increased the amount of T?RI at the cell surface. This effect was inhibited by a dominant-negative mutant of Rab11, suggesting that CIN85 promoted recycling of TGF? receptors. CIN85 enhanced TGF?-stimulated Smad2 phosphorylation, transcriptional responses, and cell migration. CIN85 expression correlated with the degree of malignancy of prostate cancers. Collectively, our results reveal that CIN85 promotes recycling of TGF? receptors and thereby positively regulates TGF? signaling.

SUBMITTER: Yakymovych I

PROVIDER: S-EPMC4508896 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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CIN85 modulates TGFβ signaling by promoting the presentation of TGFβ receptors on the cell surface.

Yakymovych Ihor I Yakymovych Mariya M Zang Guangxiang G Mu Yabing Y Bergh Anders A Landström Maréne M Heldin Carl-Henrik CH

The Journal of cell biology 20150713 2

Members of the transforming growth factor β (TGFβ) family initiate cellular responses by binding to TGFβ receptor type II (TβRII) and type I (TβRI) serine/threonine kinases, whereby Smad2 and Smad3 are phosphorylated and activated, promoting their association with Smad4. We report here that TβRI interacts with the SH3 domains of the adaptor protein CIN85 in response to TGFβ stimulation in a TRAF6-dependent manner. Small interfering RNA-mediated knockdown of CIN85 resulted in accumulation of TβRI ...[more]

PMID: 26169354

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Dataset Information

CIN85 modulates TGF? signaling by promoting the presentation of TGF? receptors on the cell surface.

Publications

CIN85 modulates TGFβ signaling by promoting the presentation of TGFβ receptors on the cell surface.

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