Focal adhesion kinase (pp125FAK) is tyrosine phosphorylated after engagement of alpha 4 beta 1 and alpha 5 beta 1 integrins on human T-lymphoblastic cells.
pp125FAK is a novel protein tyrosine kinase associated with focal adhesions. It has been shown that ligation of VLA beta 1 integrins on a number of cell types enhanced tyrosine phosphorylation and kinase activity of pp125FAK. Cellular transformation by retroviral oncogene products or mitogenic neuropeptides also result in the activation of this kinase. On the basis of these observations, pp125FAK has been proposed to be a key regulatory molecule connecting cell adhesion, transformation, and growth. We have previously shown that ligation of VLA beta 1 integrins induced CD3-dependent T cell proliferation and stimulated tyrosine phosphorylation of a molecular mass with a 105-kDa protein (pp105). Here we report that engagement of alpha 4 beta 1 and alpha 5 beta 1 integrins by adherence to their respective ligands stimulated tyrosine phosphorylation of 105- to 120-kDa proteins (pp105 and pp120, respectively) in human H9 T-lymphoblastic cells. At least one component of the 105- to 120-kDa proteins was found to be tyrosine-phosphorylated pp125FAK. While kinetics of adherence-dependent tyrosine phosphorylation of pp120/pp125FAK and pp105 are closely similar, pp105 appeared to be distinct from pp125FAK. Given T cell costimulation induced by VLA beta 1 integrins and the putative functional role of pp125FAK in cell growth, tyrosine phosphorylation of these two distinct proteins may be involved in T cell activation and proliferation.
Nojima
Y
Y
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Tachibana
K
K
Sato
T
T
Schlossman
S F
SF
Morimoto
C
C
D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000502:physiology; D010766:Phosphorylation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017469:Receptors, Fibronectin; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; D008024:Ligands; D017469:Receptors, Fibronectin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human