PubMed ID

18426911

UMMS Affiliation

Program in Molecular Medicine

Date

4-23-2008

Document Type

Article

Subjects

1-Phosphatidylinositol 3-Kinase; 3T3-L1 Cells; Actins; Adipocytes; Animals; Carrier Proteins; Cell Membrane Structures; Cells, Cultured; Enzyme Activation; Fibroblasts; Humans; Immunoprecipitation; Insulin; Mice; Myosins; Paxillin; Phosphotyrosine; Protein Binding; Protein Kinases; Protein Structure, Tertiary; Proto-Oncogene Proteins c-akt; Sirolimus

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Insulin signaling through phosphatidylinositol 3-kinase (PI 3-kinase) activates the protein kinase Akt through phosphorylation of its threonine 308 and serine 473 residues by the PDK1 protein kinase and the Rictor-mammalian target of rapamycin complex (mTORC2), respectively. Remarkably, we show here that the Rictor protein is also present in cultured adipocytes in complexes containing Myo1c, a molecular motor that promotes cortical actin remodeling. Interestingly, the Rictor-Myo1c complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Furthermore, while RNA interference-directed silencing of Rictor results in the expected attenuation of Akt phosphorylation at serine 473, depletion of Myo1c is without effect. In contrast, loss of either Rictor or Myo1c inhibits phosphorylation of the actin filament regulatory protein paxillin at tyrosine 118. Furthermore, Myo1c-induced membrane ruffling of 3T3-L1 adipocytes is also compromised following Rictor knockdown. Interestingly, neither the mTORC2 inhibitor rapamycin nor the PI 3-kinase inhibitor wortmannin affects paxillin tyrosine 118 phosphorylation. Taken together, our findings suggest that the Rictor-Myo1c complex is distinct from mTORC2 and that Myo1c, in conjunction with Rictor, participates in cortical actin remodeling events.

Rights and Permissions

Citation: Mol Cell Biol. 2008 Jul;28(13):4215-26. Epub 2008 Apr 21. Link to article on publisher's site

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Link to Article in PubMed