Proceedings of the National Academy of Sciences · 1992 · 1.4K citations · 28 references
Life SciencesCell BiologyMolecular BiologyCell SignalingOncogenesSignal TransductionFocal AdhesionsOncogenic VirusesProtein Kinase CascadesProtein LocalizationProtein PhosphorylationViral OncogenesCell Growth RegulationFocal Adhesion ComplexesImmunofluorescence StainingKinase Substrate SpecificityOncogenic TransformationProtein Tyrosine PhosphorylationTyrosine Phosphorylation SignalingViral Oncoproteins
The oncogenic Rous sarcoma virus protein pp60v‑src drives cell growth by its intrinsic tyrosine‑kinase activity, increasing phosphorylation of cellular substrates. We isolated pp125, a cytoplasmic protein‑tyrosine kinase that is highly phosphorylated in pp60v‑src‑transformed cells, localizes to focal adhesions, and represents a new kinase family.
Expression of the Rous sarcoma virus-encoded oncoprotein, pp60v-src, subverts the normal regulation of cell growth, which results in oncogenic transformation. This process requires the intrinsic protein-tyrosine kinase activity of pp60v-src and is associated with an increase in tyrosine phosphorylation of a number of cellular proteins, candidate substrates for pp60v-src. We report here the isolation of a cDNA encoding a protein, pp125, that is a major phosphotyrosine-containing protein in untransformed chicken embryo cells and exhibits an increase in phosphotyrosine in pp60v-src-transformed chicken embryo cells. This cDNA encodes a cytoplasmic protein-tyrosine kinase which, based upon its predicted amino acid sequence and structure, is the prototype for an additional family of protein-tyrosine kinases. Immunofluorescence localization experiments show that pp125 is localized to focal adhesions; hence, we suggest the name focal adhesion kinase.
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