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Phosphoproteomic Analysis Identifies Dynamic Regulation of Caveolin‐1 Phosphorylation and Caveolae Formation by mTORC2 in Bladder Cancer Cells
Author(s) -
Hau Andrew,
Gupta Sounak,
Leivo Mariah,
Zhou Weidong,
Hodge Alex,
Wulfkuhle Julie,
Conkright Brian,
Bhuvaneshwar Krithika,
Rao Shruti,
Madhavan Subha,
Nakashima Kazufumi,
Petricoin Emanuel
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.660.4
Subject(s) - mtorc2 , pi3k/akt/mtor pathway , microbiology and biotechnology , caveolae , protein kinase b , biology , phosphorylation , cell migration , motility , mechanistic target of rapamycin , signal transduction , chemistry , cancer research , mtorc1 , cell , biochemistry
The mammalian target of rapamycin (mTOR) and associated PI3K/AKT/mTOR signaling pathway is commonly upregulated in cancer, including bladder. We previously described that mTOR complex 2 (mTORC2) is a critical regulator of bladder cancer cell migration and invasion, but the precise mechanisms by which mTORC2 regulates these processes are poorly defined. Using a dual mass‐spectrometry (MS) and reverse‐phase protein array (RPPA) proteomics screening approach to reveal novel downstream phosphoprotein targets of mTORC2 in J82 and T24 bladder cancer cells, we identified 26 and 22 significantly altered biological functions putatively upregulated or down‐regulated, respectively, by mTORC2. Represented among these functions are phosphoproteins involved in regulating cell morphology, cellular assembly and organization, cell and focal adhesion, cytoskeletal rearrangement, cellular motility and others not previously linked to mTORC2 activity. Validation of a subset of these proteins revealed the ability of mTORC2 to regulate caveolin‐1 (CAV‐1) localization and dynamic phosphorylation of CAV‐1 on Y14. Regulation of CAV‐1 activity also altered the abundance of caveolae, which are specialized lipid raft invaginations of the plasma membrane that play a critical role in cell signaling pathways associated with cell and focal adhesion, and cell motility. Our results have demonstrated the utility of proteomics‐based analyses for novel elucidation of protein targets of mTORC2. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .