The reference OMIM entry for this protein is 609022

Rapamycin-insensitive companion of mtor; rictor
Avo3, s. cerevisiae, homolog of; avo3
Kiaa1999

DESCRIPTION

RICTOR and MTOR (FRAP1; 601231) are components of a protein complex that integrates nutrient- and growth factor-derived signals to regulate cell growth (Sarbassov et al., 2004).

CLONING

By sequencing clones obtained from a size-fractionated brain cDNA library, Ohara et al. (2002) cloned KIAA1999. RT-PCR ELISA detected intermediate and relatively uniform expression in all adult and fetal tissues and specific brain regions examined. By sequencing peptides obtained from purified human RICTOR, followed by database analysis and RT-PCR, Sarbassov et al. (2004) cloned RICTOR cDNA. The deduced 1,708-amino acid protein has a calculated molecular mass of 192 kD. RICTOR contains evolutionarily conserved sequences, notably an N-terminal region of about 200 amino acids and several smaller regions, including a repeated block of 20 amino acids. Jacinto et al. (2004) cloned mouse Rictor, which they called Avo3. The deduced protein contains 1,708 amino acids. A 9.5-kb transcript was detected in all tissues examined, with higher levels in skeletal muscle, kidney, placenta, and leukocytes.

GENE FUNCTION

Sarbassov et al. (2004) found that there was an inverse correlation between the relative amounts of RAPTOR (607130) and RICTOR in several human cell lines. Rapamycin treatment of human embryonic kidney cells eliminated the binding of MTOR to RAPTOR, but did not affect the interaction of MTOR with RICTOR. Knockdown of RICTOR caused accumulation of thick actin fibers throughout much of the cytoplasm in HeLa cells, loss of actin at the cell cortex, altered distribution of cytoskeletal proteins, and reduced protein kinase C (PKC)-alpha (see 176960) activity. Sarbassov et al. (2004) found that the RICTOR-containing MTOR complex contains LST8 (GBL; 612190) but not RAPTOR. Furthermore, the RICTOR-MTOR complex did not regulate the MTOR effector S6K1 (608938) and was not bound by FKBP12 (186945)-rapamycin. Sarbassov et al. (2004) concluded that the RICTOR-MTOR complex modulates the phosphorylation of PKC-alpha and the actin cytoskeleton, similar to TOR signaling in yeast. Jacinto et al. (2004) identified 2 distinct mammalian TOR complexes: TORC1, which contains TOR, LST8, and RAPTOR, and TORC2, which contains TOR, LST8, and RICTOR. Like yeast TORC2, mammalian TORC2 was rapamycin insensitive and functioned upstream of Rho GTPases to regulate the actin cytoskeleton. TORC2 did not regulate S6K activity. Knockdown of TORC2, but not TORC1, prevented paxillin (602505) phosphorylation, actin polymerization, and cell spreading. Akt/PKB (164730) activation requires the phosphorylation of ser473. Sarbassov et al. (2005) showed that in Drosophila and in human cells TOR (FRAP1; 601231) and its associated protein rictor are necessary for ser473 phosphorylation, and that a reduction in rictor or mTOR expression inhibited an AKT/PKB effector. The rictor-mTOR complex directly phosphorylated Akt/PKB on ser473 in vitro and facilitated thr308 phosphorylation by PDK1 (605213).

MAPPING

By genomic sequence analysis, Ohara et al. (2002) mapped the RICTOR gene to chromosome 5.

ANIMAL MODEL

Yang et al. (2006) found that Rictor knockout in mice was embryonic lethal. Rictor -/- embryos had no detectable Akt phosphorylation on ser473 and greatly reduced Akt phosphorylation on thr308. Western blot analysis showed that phosphorylation of multiple Akt substrates was decreased in Rictor -/- embryos. Yang et al. (2006) concluded th ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 609022 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).