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Synonyms:2610315D21Rik, AI327068, Flat, Flat-Top, FLJ44809, FRAP, FRAP1, FRAP2, FRB, MGC118056, MTOR, RAFT1, RAPT1

mTOR Pathway

The mTOR pathway involves the regulation of a protein kinase variously known as: FKBP12-rapamycin-associated protein (FRAP); mammalian target of rapamycin (mTOR) or rapamycin and FKBP12 target 1 (RAFT1) and its downstream effectors. This kinase is a component of two functional complexes; TORC1 and TORC2. TORC1 is the rapamycin-sensitive mTOR complex responsible for regulation of protein translation initiation and efficiency. TORC1 contains; mTOR, the kinase; raptor (KOG1), a scaffold protein that mediates the association of mTOR with its substrates; LST8; and Tco89.

TORC1 is sensitive to nutrients, especially amino acids such as leucine. This sensitivity involves the small GTPase Ras homologue, Rheb. TORC1 is activated by phosphatidic acid (PA) that results from the induction of phospholipase D by mechanical stimuli. TORC1 is activated by growth factor receptors through the phosphatidylinositol-3-kinase (PI3K); protein kinase D1 (PDK1); protein kinase B (Akt/PKB) pathway.

Activated mTOR (TORC1) phosphorylates protein phosphatase 2A (PP2A), p70S6K (S6K1) and eIF4E-BP (PHAS-1). Phosphorylation of PP2A prevents the dephosphorylation of p70S6K and eIF4E-BP. The phosphorylation of eIF4E-BP releases eIF4E which can then participate in the formation of the protein translation complex involving capped mRNAs. Phosphorylated p70S6K can phosphorylate the ribosomal S6 subunit which enhances the translation of 5'-terminal oligopyrimidine (TOP)-mRNAs. Enhanced translation of TOP-mRNAs leads to increased synthesis of proteins required for protein synthetic machinery. The combined effect of increased translation initiation and increased ribosomal and other translational proteins leads to enhanced protein synthesis and cell growth.