The related adhesion focal tyrosine kinase is tyrosine-phosphorylated after beta1-integrin stimulation in B cells and binds to p130cas.
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.
Astier
A
A
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Avraham
H
H
Manie
S N
SN
Groopman
J
J
Canty
T
T
Avraham
S
S
Freedman
A S
AS
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
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