Zimmer Y Vaseva AV Medová M Streit B Blank-Liss W Greiner RH Schiering N Aebersold DM 2010 Point mutations emerge as one of the rate-limiting steps in tumor response to small molecule inhibitors of protein kinases. Here we characterized the response of the MET mutated variants, V1110I, V1238I, V1206L and H1112L to the small molecule SU11274. Our results reveal a distinct inhibition pattern of the four mutations with IC(50) values for autophosphorylation inhibition ranging between 0.15 and 1.5muM. Differences were further seen on the ability of SU11274 to inhibit phosphorylation of downstream MET transducers such as AKT, ERK, PLCgamma and STAT3 and a variety of MET-dependent biological endpoints. In all the assays, H1112L was the most sensitive to SU11274, while V1206L was less affected under the used concentration range. The differences in responses to SU11274 are discussed based on a structural model of the MET kinase domain. https://sonar.ch/global/documents/1234 eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.canlet.2009.08.017 info:eu-repo/semantics/altIdentifier/pmid/19783361 Cancer letters. - 2010 Animals Blotting, Western Cell Adhesion Cell Cycle Indoles Mice Mitogen-Activated Protein Kinase 3 Mutation NIH 3T3 Cells Oncogene Protein v-akt Phospholipase C gamma Phosphorylation Piperazines Protein Conformation Proto-Oncogene Proteins c-met STAT3 Transcription Factor Sulfonamides Wound Healing Differential inhibition sensitivities of MET mutants to the small molecule inhibitor SU11274. http://purl.org/coar/resource_type/c_6501