title: The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1-integrin stimulation in B cells and binds to p130cas.
abstract: Integrin ligation initiates intracellular signaling events, among which are the activation of protein tyrosine kinases. The related adhesion focal tyrosine kinase (RAFTK), also known as PYK2 and CAKbeta, is a tyrosine kinase that is homologous to the focal adhesion kinase (FAK) p125FAK. The structure of RAFTK is similar to p125FAK in that it lacks a transmembrane region, does not contain Src homology 2 or 3 domains, and has a proline-rich region in its C terminus. Here we report that RAFTK is a target for beta1-integrin-mediated tyrosine phosphorylation in both transformed and normal human B cells. Ligation of the B cell antigen receptor also induced tyrosine phosphorylation of RAFTK. Phosphorylation of RAFTK following integrin- or B cell antigen receptor-mediated stimulation was decreased by prior treatment of cells with cytochalasin B, indicating that this process was at least partially cytoskeleton-dependent. One of the tyrosine-phosphorylated substrates after integrin stimulation in fibroblasts is p130cas, which can associate with p125FAK. RAFTK also interacted constitutively with p130cas in B cells, since p130cas was detected in RAFTK immunoprecipitates. Although the function of RAFTK remains unknown, these data suggest that RAFTK may have a significant function in integrin-mediated signaling pathways in B cells.
authors.affiliation: Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Astier
authors.forename: H
authors.initials: H
authors.lastname: Avraham
authors.forename: S N
authors.initials: SN
authors.lastname: Manie
authors.forename: J
authors.initials: J
authors.lastname: Groopman
authors.forename: T
authors.initials: T
authors.lastname: Canty
authors.forename: S
authors.initials: S
authors.lastname: Avraham
authors.forename: A S
authors.initials: AS
authors.lastname: Freedman
mesh_terms: D001402:B-Lymphocytes / Q000201:enzymology*; D050719:Crk-Associated Substrate Protein; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D051418:Focal Adhesion Kinase 2; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D014066:Palatine Tonsil / Q000166:cytology; D010750:Phosphoproteins / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction
chemical_list: C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D019012:Integrin beta1; D046911:Macromolecular Substances; D010750:Phosphoproteins; D011506:Proteins; D011947:Receptors, Antigen, B-Cell; D050717:Retinoblastoma-Like Protein p130; D019000:Phosphotyrosine; D003571:Cytochalasin B; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2