Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:A Rictor-Myo1c complex participates in dynamic cortical actin events in 3T3-L1 adipocytes. 1842 11

The present study investigated the clinical significance of miR-138 in patients with malignant melanoma (MM), which has previously been associated with tumor growth. In patients with MM, we found that the expression of miR-138 was significantly downregulated when compared with healthy control subjects. Overexpression of miR-138 in the human melanoma cell line A2058 inhibited cell proliferation and induced cell apoptosis, and increased caspase-3 and Bax protein expression when compared with a negative control group. Meanwhile, miR-138 overexpression promoted cell autophagy, induced LC3 protein expression, and suppressed the PI3K/AKT/mTOR signaling pathway and PDK1 protein expression in A2058 cells. LY294002, an inhibitor of PI3K, suppressed PI3K/AKT/mTOR signaling, induced apoptosis, inhibited cell proliferation, increased caspase-3 and Bax protein expression, and decreased PDK1 protein expression in A2058 cells following miR-138 overexpression. Collectively, our findings indicate the clinical significance of miR-138 in patients with MM through its targeting of PDK1 expression in the PI3K/AKT/mTOR autophagy signaling pathway.
 ...
PMID:Clinical significance of miR-138 in patients with malignant melanoma through targeting of PDK1 in the PI3K/AKT autophagy signaling pathway. 2873 Nov 79