title: The lipid raft-anchored adaptor protein Cbp controls the oncogenic potential of c-Src.
abstract: The tyrosine kinase c-Src is upregulated in various human cancers irrespective of its negative regulator Csk, but the regulatory mechanisms remain unclear. Here, we show that a lipid raft-anchored Csk adaptor, Cbp/PAG, is directly involved in controlling the oncogenicity of c-Src. Using Csk-deficient cells that can be transformed by c-Src overexpression, we found that Cbp expression is markedly downregulated by c-Src activation and re-expression of Cbp efficiently suppresses c-Src transformation as well as tumorigenesis. Cbp-deficient cells are more susceptible to v-Src transformation than their parental cells. Upon phosphorylation, Cbp specifically binds to activated c-Src and sequesters it in lipid rafts, resulting in an efficient suppression of c-Src function independent of Csk. In some human cancer cells and tumors, Cbp is downregulated and the introduction of Cbp significantly suppresses tumorigenesis. These findings indicate a potential role for Cbp as a suppressor of c-Src-mediated tumor progression.
authors.affiliation: Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Chitose
authors.initials: C
authors.lastname: Oneyama
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hikita
authors.forename: Kengo
authors.initials: K
authors.lastname: Enya
authors.forename: Marc-Werner
authors.initials: MW
authors.lastname: Dobenecker
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Saito
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Nada
authors.forename: Alexander
authors.initials: A
authors.lastname: Tarakhovsky
authors.forename: Masato
authors.initials: M
authors.lastname: Okada
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002458:Cell Fractionation; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D018014:Gene Transfer Techniques; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases
chemical_list: D008565:Membrane Proteins; C498709:Pag1 protein, mouse; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human