title: Identification of rictor as a novel substrate of Polo-like kinase 1.
abstract: Plk1 has been essentially described as a critical regulator of many mitotic events. However, increasing evidence supports the notion that its molecular functions are not restricted to the cell cycle. In particular, recent reports suggest the existence of a molecular and functional link between Plk1 and the mammalian target of rapamycin (mTOR) pathway, which controls cell growth and proliferation via the raptor-mTOR (TORC1) and rictor-mTOR (TORC2) protein complexes. Herein, we have identified rapamycin-insensitive companion of mTOR (Rictor), a core component of mTORC2, as a new Plk1 substrate and have shown that Plk1 phosphorylates Rictor at Ser1162 in vitro and in vivo. Surprisingly, cells expressing the unphosphorylatable mutant (S1162A) of Rictor did not show any effect on well characterized canonical PI3K-mTOR pathway. However, we found that cells expressing the unphosphorylatable form of Rictor have an elevated level of mSin1 isoform (mSin1.5). Considering that mSin1.5-containing mTORC2 was reported to associate with stress signaling, we propose that phosphorylation of Rictor at Ser1162 by Plk1 might be involved in a novel signaling pathway by regulating the mSin1.5-defined mTORC2.
authors.affiliation: a Department of Biochemistry ; Purdue University ; West Lafayette , IN USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Shao
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D013379:Substrate Specificity; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D010768:Phosphoserine; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D058570:TOR Serine-Threonine Kinases; D000097869:Polo-Like Kinase 1; C492571:RICTOR protein, human
keywords: 4E-BP1, eIF4E-binding protein 1; GST, glutathione S-transferase; IB, immunoblotting.; IP, immunoprecipitation; PDK1, 3-phophoinositide-dependent protein kinase 1 (PDK1); Plk1; Plk1, polo-like kinase 1; Raptor, regulatory-associated protein of mTOR; Rictor; Rictor, rapamycin-insensitive companion of mTOR; S6K, S6 Kinase; WT, wild type; aa, amino acids; cell cycle; mSin1; mSin1, mammalian stress-activated map kinase-interacting protein 1 (mSin1); mTOR, mammalian target of rapamycin; mTORC; mTORC1, mTOR complex 1; mTORC2, mTOR complex 2; phosphorylation