Gene interactions and pathways from curated databases and text-mining
Cancer Res 2008, PMID: 18339839

Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival.

McDonald, Paul C; Oloumi, Arusha; Mills, Julia; Dobreva, Iveta; Maidan, Mykola; Gray, Virginia; Wederell, Elizabeth D; Bally, Marcel B; Foster, Leonard J; Dedhar, Shoukat

An unbiased proteomic screen to identify integrin-linked kinase (ILK) interactors revealed rictor as an ILK-binding protein. This finding was interesting because rictor, originally identified as a regulator of cytoskeletal dynamics, is also a component of mammalian target of rapamycin complex 2 (mTORC2), a complex implicated in Akt phosphorylation. These functions overlap with known ILK functions. Coimmunoprecipitation analyses confirmed this interaction, and ILK and rictor colocalized in membrane ruffles and leading edges of cancer cells. Yeast two-hybrid assays showed a direct interaction between the NH(2)- and COOH-terminal domains of rictor and the ILK kinase domain. Depletion of ILK and rictor in breast and prostate cancer cell lines resulted in inhibition of Akt Ser(473) phosphorylation and induction of apoptosis, whereas, in several cell lines, depletion of mTOR increased Akt phosphorylation. Akt and Ser(473)P-Akt were detected in ILK immunoprecipitates and small interfering RNA-mediated depletion of rictor, but not mTOR, inhibited the amount of Ser(473)P-Akt in the ILK complex. Expression of the NH(2)-terminal (1-398 amino acids) rictor domain also resulted in the inhibition of ILK-associated Akt Ser(473) phosphorylation. These data show that rictor regulates the ability of ILK to promote Akt phosphorylation and cancer cell survival.

Diseases/Pathways annotated by Medline MESH: Breast Neoplasms, Neoplasms
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Text Mining Data

Akt → Rictor: " Rictor and integrin linked kinase interact and regulate Akt phosphorylation and cancer cell survival "

Akt → integrin linked kinase: " Rictor and integrin linked kinase interact and regulate Akt phosphorylation and cancer cell survival "

Akt ⊣ mTOR: " Depletion of ILK and rictor in breast and prostate cancer cell lines resulted in inhibition of Akt Ser ( 473 ) phosphorylation and induction of apoptosis, whereas, in several cell lines, depletion of mTOR increased Akt phosphorylation "

Manually curated Databases

  • IRef Intact Interaction: RICTOR — MTOR (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: ILK — RICTOR (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: ILK — RICTOR (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: ILK — RICTOR (physical association, two hybrid)
  • IRef Intact Interaction: ILK — RICTOR (physical association, fluorescence microscopy)
  • IRef Intact Interaction: Complex of MTOR-ILK-RICTOR-RICTOR-ILK-MTOR (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of LIMS1-RICTOR-ILK (association, anti tag coimmunoprecipitation)
  • NCI Pathway Database Integrin-linked kinase signaling: RICTOR (RICTOR) → ILK/RICTOR complex (ILK-RICTOR) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Integrin-linked kinase signaling: RICTOR (RICTOR) → ILK (ILK) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Integrin-linked kinase signaling: ILK/RICTOR complex (ILK-RICTOR) → ILK (ILK) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database Integrin-linked kinase signaling: ILK/RICTOR complex (ILK-RICTOR) → AKT1 (AKT1) (modification, activates)
    Evidence: assay, physical interaction
In total, 9 gene pairs are associated to this article in curated databases