| http://purl.uniprot.org/citations/32576681 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32576681 | http://www.w3.org/2000/01/rdf-schema#comment | "Receptor tyrosine kinases (RTKs) are often overexpressed or mutated in cancers and drive tumor growth and metastasis. In the current model of RTK signaling, including that of MET, downstream phosphatidylinositol 3-kinase (PI3K) mediates both cell proliferation and cell migration, whereas the small guanosine triphosphatase (GTPase) Rac1 mediates cell migration. However, in cultured NIH3T3 and glioblastoma cells, we found that class I PI3K mediated oncogenic MET-induced cell migration but not anchorage-independent growth. In contrast, Rac1 regulated both processes in distinct ways. Downstream of PI3K, Rac1 mediated cell migration through its GTPase activity, whereas independently of PI3K, Rac1 mediated anchorage-independent growth in a GTPase-independent manner through an adaptor function. Through its RKR motif, Rac1 formed a complex with the kinase mTOR to promote its translocation to the plasma membrane, where its activity promoted anchorage-independent growth of the cell cultures. Inhibiting mTOR with rapamycin suppressed the growth of subcutaneous MET-mutant cell grafts in mice, including that of MET inhibitor-resistant cells. These findings reveal a GTPase-independent role for Rac1 in mediating a PI3K-independent MET-to-mTOR pathway and suggest alternative or combined strategies that might overcome resistance to RTK inhibitors in patients with cancer."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.org/dc/terms/identifier | "doi:10.1126/scisignal.aba8627"xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/author | "Zhang C."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/author | "Menard L."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/author | "Clarke P.A."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/author | "Hervieu A."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/author | "Heuss S.F."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/author | "Kermorgant S."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/author | "Joffre C."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/author | "Barrow-McGee R."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/name | "Sci Signal"xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/pages | "eaba8627"xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/title | "A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration."xsd:string |
| http://purl.uniprot.org/citations/32576681 | http://purl.uniprot.org/core/volume | "13"xsd:string |
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