Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation

  title={Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation},
  author={Jun-Lin Guan and David Shalloway},
INCREASING evidence indicates that the integrin family of cell adhesion receptors can transduce biochemical signals from the extracellular matrix to the cell interior to modulate cell growth and differentiation1. We have shown that integrin/ligand interactions can trigger tyrosine phosphorylation of a protein of Mr 120,000 (pp120), so it is possible that signal transduction by integrins might involve activation of intracellular protein tyrosine kinases as an early event in cell binding to the… 
Matrix/Integrin Interaction Activates the Mitogen-activated Protein Kinase, p44 and p42(*)
It is reported that p44 and p42 mitogen-activated protein (MAP) kinases are rapidly phosphorylated on tyrosine residues upon adhesion of human skin fibroblasts to fibronectin or upon cross-linking of β1 integrins with antibody and that the integrity of the actin cytoskeleton is essential in this process.
Focal adhesion kinase pp125FAK and the beta 1 integrin subunit are constitutively complexed in HaCaT cells.
It is shown that in HaCaT cells (a human keratinocyte derived cell line) the integrin beta 1 subunit is associated with tyrosine kinase pp125FAK, and this association was observed in ECM-adherent cells and nonadherence cells and is independent of tyrosinesine phosphorylation.
The association of focal adhesion kinase with a 200-kDa protein that is tyrosine phosphorylated in response to platelet-derived growth factor.
The association of FAK with a 200-kDa protein (pp200) that is tyrosine phosphorylated in response to PDGF stimulation in NIH 3T3 cells is described, which may also be involved in growth-factor-induced cellular effects such as the modulation of cell adhesion or cell migration via cytoskeletal reorganization or disruption of focal adhesions.
Interaction of Focal Adhesion Kinase with Cytoskeletal Protein Talin (*)
The interaction of cells with extracellular matrix proteins plays a critical role in a variety of biological processes. Recent studies suggest that cell-matrix interactions mediated by integrins can
Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility.
Focal adhesion kinase (FAK) was first described in 1992 as a novel nonreceptor protein-tyrosine kinase localized prominently within focal adhesions, suggesting a signaling role in regulating cell
Tyrosine Phosphorylation of p130Cas and Cortactin Accompanies Integrin-mediated Cell Adhesion to Extracellular Matrix (*)
The results suggest that ligand binding of integrins regulates the tyrosine phosphorylation state of multiple docking proteins, which may mediate anchorage dependence of growth and their misregulation in v-src-transformed and other tumorigenic cells may be responsible for the anchorage independence of such cells.
Role of focal adhesion kinase in signaling by the extracellular matrix.
  • J. Zhao, J. Guan
  • Biology
    Progress in molecular and subcellular biology
  • 2000
Integrin-mediated cell adhesion can regulate gene expression, intracellular pH and calcium, phospholipid metabolites, small GTPase, protein serine/threonine kinases, and protein tyrosine phosphorylation.
Tyrosine Phosphorylation of Focal Adhesion Kinase Stimulated by Hepatocyte Growth Factor Leads to Mitogen-activated Protein Kinase Activation*
It is demonstrated that HGF stimulates the association of FAK with Grb2 in vitro and in intact cells and provided evidence that FAK might contribute to the activation of mitogen-activated protein kinase through Ras in HGF signaling by functioning as an adapter molecule.
Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn.
It is reported here that overexpression of FAK in CHO cells increased their migration on fibronectin, and a mutation of the major autophosphorylation site Y397 in FAK abolished its ability to stimulate cell migration, while phosphorylation in a kinase-defective FAK by endogenous FAK led to increased migration.
Role of focal adhesion kinase in integrin signaling.
  • J. Guan
  • Biology, Chemistry
    The international journal of biochemistry & cell biology
  • 1997


Signal transduction by integrins: increased protein tyrosine phosphorylation caused by clustering of beta 1 integrins.
It is postulated that the integrin-stimulated tyrosine phosphorylation of pp130 may reflect part of an important signal transduction process between the extracellular matrix and the cell interior.
Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein.
Interaction of beta 1 integrins with extracellular ligands (fibronectin or antibodies) triggers phosphorylation of an intracellular 120-kDa protein, pp120, that may be involved in the responses of cells to attachment.
pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions.
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-transformedChicken embryo cells is reported.
Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases.
Monoclonal antibodies are generated to detect several of the same tyrosine phosphoproteins in chicken embryo fibroblasts transformed by avian retroviruses Y73 and CT10, encoding the yes and crk oncogenes, respectively.
Novel tyrosine kinase substrates from Rous sarcoma virus-transformed cells are present in the membrane skeleton
A new approach to both the identification of membrane skeletal proteins in fibroblasts and changes that occur upon transformation by an activated tyrosine kinase is offered.
A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants.
In Xenopus oocytes, this protein maintains normal p21 in a biologically inactive, GDP-bound state through its effect on GTPase activity, and it appears that the major effect of position 12 mutations is to prevent this protein from stimulating p21 GTP enzyme activity, thereby allowing these mutants to remain in the active GTP- bound state.
Interaction of serum and cell spreading affects the growth of neoplastic and non-neoplastic fibroblasts.
It is found that more spreading increased net growth of both neoplastic and non-neoplastic cells, while less spreading depressed growth, and it appears that the sensitivity of cells to humoral factors is governed by cell spreading.
Isolation of antibodies for phosphotyrosine by immunization with a v-abl oncogene-encoded protein.
  • J. Wang
  • Biology
    Molecular and cellular biology
  • 1985
The usefulness of these antibodies was demonstrated by the detection of previously unidentified tyrosine-phosphorylated proteins in v-src, v-abl-, and v-erbB-transformed cell lines.