The Association of Focal Adhesion Kinase with a 200‐kDa Protein that is Tyrosine Phosphorylated in Response to Platelet‐Derived Growth Factor

Chen, Hong Chen; Guan, Jun

doi:10.1111/j.1432-1033.1996.00495.x

Cited by 13 publications

(10 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the face of platelet-derived growth factor stimulation, there was a strong association of FAK with pp200 in NIH 3T3 cells. This association was independent of cell adhesion and was therefore thought to be involved with growth factor-induced cellular effects [53]. Sieg et al [54] have also shown that FAK associates with activated PDGF-and EGF-receptors (PDGFR and EGFR) signaling complexes and established that FAK was an important receptorproximal link between growth factor receptor and integrin signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the focal adhesion kinase and vascular endothelial growth factor receptor‐3 interaction leads to decreased survival in human neuroblastoma cell lines

Beierle

Stewart

et al. 2012

Molecular Carcinogenesis

View full text Add to dashboard Cite

Neuroblastoma continues to be a devastating childhood solid tumor and is responsible for over 15% of all childhood cancer related deaths. Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor-3 (VEGFR-3) are protein tyrosine kinases that are overexpressed in a number of human cancers, including neuroblastoma. These two kinases can directly interact and provide survival signals to cancer cells. In this study, we utilized siRNA to VEGFR-3 to demonstrate the biologic importance of this kinase in neuroblastoma cell survival. We also used confocal microscopy and immunoprecipitation to show that FAK and VEGFR-3 bind in neuroblastoma. Finally, employing a 12-amino-acid peptide (AV3) specific to VEGFR-3, we showed that the colocalization between FAK and VEGFR-3 could be disrupted, and that disruption resulted in decreased neuroblastoma cell survival. These studies provide insight to the FAK - VEGFR-3 interaction in neuroblastoma and demonstrate its importance in this tumor type. Focusing upon the FAK - VEGFR-3 interaction may provide a novel therapeutic target for the development of new strategies for treatment of neuroblastoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of the focal adhesion kinase and vascular endothelial growth factor receptor‐3 interaction leads to decreased survival in human neuroblastoma cell lines

Beierle

Stewart

et al. 2012

Molecular Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…There are several reports of hitherto unidentified 190 kDa phosphoproteins in PDGF‐stimulated cells, found by immunoprecipitating with anti‐FAK (Chen and Guan, 1996), anti‐αvβ3 (Bartfeld et al ., 1993) or anti‐caveolin (Liu et al ., 1996) antibodies. In each case, these proteins have been reported not to be reactive with anti‐PDGFβ‐R antibodies.…”

Section: Discussionmentioning

confidence: 99%

alpha vbeta 3 integrin associates with activated insulin and PDGFbeta receptors and potentiates the biological activity of PDGF

1997

View full text Add to dashboard Cite

(FAK) is a pathway shared by several integrins. It seems USA to be particularly important in anchorage dependence 1 Corresponding author (Frisch et al., 1996;Xu et al., 1996). Moreover, several growth factor receptors have been shown to be present in Integrin-mediated cell attachment modulates growth isolated focal adhesion complexes and in other membrane responses and growth factors regulate cell attachment.structures containing aggregated integrins (Plopper et al., Moreover, both cell attachment to extracellular matrix 1995; Miyamoto et al., 1996). and mitogenic signaling by growth factors are necessaryThe pathways that are known to be restricted to indifor the proliferation of most types of normal cells, vidual integrins include up-regulation of the anti-apoptosis suggesting that integrin and growth factor receptor protein Bcl-2 by the α5β1 integrin (Zhang et al., 1995), signaling pathways meet at some downstream point.activation of the adaptor protein Shc by α6β4 (Mainiero We report here that a small, highly tyrosine-phos et al., 1995) and, presumably by an unrelated process, by phorylated fraction of PDGFβ and insulin receptors certain other integrins (Wary et al., 1996). Moreover, the co-immunoprecipitates with the αvβ3 integrin from αvβ3 integrin interacts with the PDGF and insulin receptor cells. The integrin association requires growth factor signaling pathways (Bartfeld et al., 1993; Vuori and stimulation of the receptors. Several signaling mole- Ruoslahti, 1994). cules that are known to be associated with activatedThat the αvβ3 integrin is somehow linked to PDGF growth factor receptors were present in the αvβ3 signaling was first suggested by the finding of Bartfeld integrin complexes. Mitogenicity and chemotaxis et al. (1993) that a 190 kDa tyrosine-phosphorylated induced by PDGF-BB were enhanced in cells plated protein could be immunoprecipitated together with αvβ3 on the αvβ3 ligand vitronectin compared with cells from PDGF-BB-stimulated cells. The identity of the 190 plated on the β1 integrin ligand collagen. Thus, the kDa protein is not known. An involvement of αvβ3 in engagement of the αvβ3 integrin in cell-matrix interinsulin signaling was discovered when IRS-1, a cytoactions appears to coordinate an intense response to growth factors, helping to explain the importance of plasmic signal transduction mediator of the insulin (and this integrin for tissue regeneration, angiogenesis and insulin-like growth factor, IGF) receptors, was found to tumor metastasis.co-immunoprecipitate with αvβ3 (Vuori and Ruoslahti, Keywords: αvβ3 integrin/cell attachment/cell-matrix 1994). IRS-1 is tyrosine-phosphorylated by the activated interaction/growth factors/PDGFβ insulin (and IGF) receptor tyrosine kinases (RTK) and as a result binds a number of downstream signaling molecules (White and Kahn, 1994). The mitogenic activity of insulin is enhanced in cells that have adhered to a substrate (such

show abstract

“…We have found that this p200 is not PDGF-R, but we were not able to identify this protein that should be a cytoskeleton-associated substrate of LMW-PTP. Among proteins that: 1) have a molecular mass of about 200 kDa, 2) reside in the cytoskeleton fraction, and 3) become tyrosine-phosphorylated in response to PDGF, tensin, talin, p190GAP, and a yet unidentified p200 (24) are possible candidates to be a LMW-PTP substrate in the cRIPA fraction.…”

Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Protein-tyrosine Phosphatase Tyrosine Phosphorylation by c-Src during Platelet-derived Growth Factor-induced Mitogenesis Correlates with Its Subcellular Targeting

Cirri

Chiarugi

Taddei

et al. 1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

The low molecular weight phosphotyrosine phosphatase (LMW-PTP) is an enzyme that is involved in the early events of platelet-derived growth factor (PDGF) receptor signal transduction. Our previous results have shown that LMW-PTP is able to specifically bind and dephosphorylate activated PDGF receptor, thus modulating PDGF-induced mitogenesis. In particular LMW-PTP is involved in pathways that regulate the transcription of the immediately early genes myc and fos in response to growth factor stimulation. In this study we have established that, in nontransformed NIH3T3 cells, LMW-PTP exists constitutively in cytosolic and cytoskeleton-associated localization and that, after PDGF stimulation, c-Src is able to bind and to phosphorylate LMW-PTP only in the cytoskeletonassociated fraction. As a consequence of its tyrosine phosphorylation, LMW-PTP significantly increases its catalytic activity. After PDGF stimulation these two LMW-PTP pools act on distinct substrates, contributing in different manners to the PDGF receptor signaling. The cytoplasmic LMW-PTP fraction exerts its well known action on activated PDGF receptor. On the other hand we have now demonstrated that the cytoskeleton-associated LMW-PTP acts specifically on a few not yet identified proteins that become tyrosinephosphorylated in response to the PDGF receptor activation. Finally, these two LMW-PTP pools markedly differ in the timing of the processes in which they are involved. The cytoplasmic LMW-PTP pool exerts its action within a few minutes from PDGF receptor activation (short term action), while tyrosine phosphorylation of cytoskeleton-associated LMW-PTP lasts for more than 40 min (long term action). In conclusion LMW-PTP is a striking example of an enzyme that exerts different functions and undergoes different regulation in consequence of its subcellular localization.

show abstract

The Association of Focal Adhesion Kinase with a 200‐kDa Protein that is Tyrosine Phosphorylated in Response to Platelet‐Derived Growth Factor

Cited by 13 publications

References 45 publications

Inhibition of the focal adhesion kinase and vascular endothelial growth factor receptor‐3 interaction leads to decreased survival in human neuroblastoma cell lines

Inhibition of the focal adhesion kinase and vascular endothelial growth factor receptor‐3 interaction leads to decreased survival in human neuroblastoma cell lines

alpha vbeta 3 integrin associates with activated insulin and PDGFbeta receptors and potentiates the biological activity of PDGF

Low Molecular Weight Protein-tyrosine Phosphatase Tyrosine Phosphorylation by c-Src during Platelet-derived Growth Factor-induced Mitogenesis Correlates with Its Subcellular Targeting

Contact Info

Product

Resources

About