title: Breast cancer cell line proliferation blocked by the Src-related Rak tyrosine kinase.
abstract: Rak is a 54 kDa protein tyrosine kinase originally isolated from breast cancer cells and expressed in epithelial cells. It resembles the protooncogene Src structurally but lacks an amino-terminal myristylation site and localizes to the nuclear and perinuclear regions of the cell. We report here that expression of Rak in 2 different breast cancer cell lines inhibits growth and causes G(1) arrest of the cell cycle. This growth inhibition is kinase-dependent but does not require the Rak SH2 or SH3 domain. Rak also binds to the pRb tumor-suppressor protein but inhibits growth even in cells that lack pRb. These results suggest that Rak regulates cell growth by phosphorylating perinuclear proteins and has a function that is distinct from the Src-related kinase family.
authors.affiliation: Department of Surgery, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Meyer
authors.forename: LiHui
authors.initials: L
authors.lastname: Xu
authors.forename: Jinli
authors.initials: J
authors.lastname: Chang
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
authors.forename: Rolf J
authors.initials: RJ
authors.lastname: Craven
authors.forename: William G
authors.initials: WG
authors.lastname: Cance
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002455:Cell Division; D005434:Flow Cytometry; D016193:G1 Phase; D006801:Humans; D018613:Microscopy, Confocal; D009154:Mutation; D009363:Neoplasm Proteins; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human