The Adaptor Protein Shc Couples a Class of Integrins to the Control of Cell Cycle Progression

Wary, Kishore K.; Mainiero, Fabrizio; Isakoff, Steven J.; Marcantonio, Eugene E.; Giancotti, Filippo G.

doi:10.1016/s0092-8674(00)81392-6

Cited by 711 publications

(672 citation statements)

References 47 publications

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“…Recent studies supporting the second possibility have shown that engagement of a subset of b 1 and a v integrins by ®bronectin stimulates the MAP kinase pathway and cell cycle progression via Shc; conversely, engagement of di erent integrins by other extracellular glycoproteins not linked to Shc, does not activate the MAP kinase pathway, and leads to cell cycle exit and apoptosis (Wary et al, 1996). Therefore, the array of glycoproteins displayed on a cell's surface determines the particular intracellular growth pathways that are stimulated, and it is thus critically important in sustaining normal cellular growth characteristics.…”

Section: Resultsmentioning

confidence: 99%

Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

et al. 1998

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The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor (HGF)/scatter factor are involved in the etiology and progression of a number of human cancers. Coexpression of Met and HGF in mesenchymal cells increases the tumorigenic and metastatic potential of the cells. In the studies described here, we used di erential display screening to identify changes in gene expression that are initiated by Met/HGF, and that may lead to these phenotypes. We learned that Met/ HGF signaling resulted in greatly decreased ®bronectin mRNA production in three di erent human and mouse tumor cell lines; these decreases in ®bronectin mRNA were paralleled by decreases in ®bronectin protein. We also found a progressive decrease in ®bronectin in tumor explants and metastases derived from the Met/HGF transformed cells. The absence of ®bronectin expression is a frequent cancer phenotype; our results indicate that decreases in ®bronectin correlate with, but are not essential for, MetHGF/SF-mediated tumorigenesis.

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Section: Resultsmentioning

confidence: 99%

Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

et al. 1998

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“…A number of signaling proteins have been found to be associated with the focal adhesion complexes suggesting the involvement of integrin engagement in the activation of signaling pathways. It is now generally accepted that the activation of ERK in response to integrin ligation requires Ras signaling Wary et al, 1996). Evidence is presented that certain integrins such as the laminin receptor a 6 b 4 , the lamin/collagen receptor a 1 b 1 , the ®bronectin receptor a 5 b 1 and the vitronectin receptor a v b 3 are linked to the RAS-ERK signaling pathway by the adaptor protein Shc (Wary et al, 1996;Giancotti, 1997).…”

Section: Role Of Integrins In Cell-proliferation Signaling Pathwaysmentioning

confidence: 99%

“…It is now generally accepted that the activation of ERK in response to integrin ligation requires Ras signaling Wary et al, 1996). Evidence is presented that certain integrins such as the laminin receptor a 6 b 4 , the lamin/collagen receptor a 1 b 1 , the ®bronectin receptor a 5 b 1 and the vitronectin receptor a v b 3 are linked to the RAS-ERK signaling pathway by the adaptor protein Shc (Wary et al, 1996;Giancotti, 1997). Shc is an SH2 and phosphotyrosine binding (PTB) domain adaptor protein which links tyrosinephosphorylated signal transducers to Ras (Pawson, 1995).…”

Section: Role Of Integrins In Cell-proliferation Signaling Pathwaysmentioning

confidence: 99%

“…Ligation of a 1 b 1 , a 5 b 1 and a v b 3 integrins which are all linked to Shc results in Erk activation, but ligation of other integrins does not produce this e ect, even though FAK is stimulated (Wary et al, 1996). A dominant negative mutant Shc was found to suppress ERK activation in response to integrin ligation (Wary et al, 1996), but two distinct dominant-negative mutants of FAK do not (Lin et al, 1997;Giancotti, 1997). These results indicate that Shc is necessary and su cient to link speci®c integrins to the RAS-ERK signaling pathway.…”

Section: Role Of Integrins In Cell-proliferation Signaling Pathwaysmentioning

confidence: 99%

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Signaling by integrin receptors

Kumar¹

1998

Oncogene

257

181

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Adhesive interactions are critical for the proliferation, survival and function of all cells. Integrin receptors as the major family of adhesion receptors have been the focus of study for more than a decade. These studies have tremendously enhanced our understanding of the integrin-mediated adhesive interactions and have unraveled novel integrin functions in cell survival mechanisms and in the activation of divergent signaling pathways. The signals from integrin receptors are integrated from those originating from growth factor receptors in order to organize the cytoskeleton, stimulate cell proliferation and rescue cells from matrix detachment-induced programmed cell death. These functions are critical in the regulation of multiple processes such as tissue development, in¯ammation, angiogenesis, tumor cell growth and metastasis and programmed cell death.

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“…Meanwhile, previous studies showed that expression of a v b 3 integrins promoted cellular uptake via caveolae-mediated endocytosis and that, a v b 5 expression facilitated clathrin-mediated endocytosis. [39][40][41] As the binding affinity of cRGD with a v b 3 is 10 times stronger than that with a v b 5 , it might be reasonable that caveolae-mediated endocytosis was a dominant process in the cellular uptake of cRGD-PEG-PAsp(DET) micelles. 42 In contrast to clathrin-mediated endocytosis, the internalization pathway via caveolae-mediated endocytosis is known to bypass degradative organelles and not to be associated with a decrease in pH.…”

Section: Discussionmentioning

confidence: 99%

Impact of polyplex micelles installed with cyclic RGD peptide as ligand on gene delivery to vascular lesions

et al. 2011

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Gene therapy is expected to open a new strategy for the treatment of refractory vascular diseases, so the development of appropriate gene vectors for vascular lesions is needed. To realize this requirement with a non-viral approach, cyclo(RGDfK) peptide (cRGD) was introduced to block copolymer, poly(ethylene glycol)-block-polycation carrying ethylenediamine units (PEG-PAsp(DET)). cRGD recognizes a v b 3 and a v b 5 integrins, which are abundantly expressed in vascular lesions. cRGDconjugated PEG-PAsp(DET) (cRGD-PEG-PAsp(DET)) formed polyplex micelles through complexation with plasmid DNA (pDNA) and the cRGD-PEG-PAsp(DET) micelles achieved significantly more efficient gene expression and cellular uptake as compared with PEG-PAsp(DET) micelles in endothelial cells and vascular smooth muscle cells. Intracellular tracking of pDNA showed that cRGD-PEG-PAsp(DET) micelles were internalized via caveolae-mediated endocytosis, which is associated with a pathway avoiding lysosomal degradation and that, PEG-PAsp(DET) micelles were transported to acidic endosomes and lysosomes via clathrin-mediated endocytosis. Further, in vivo evaluation in rat carotid artery with a neointimal lesion revealed that cRGD-PEGPAsp(DET) micelles realized sustained gene expression, whereas PEG-PAsp(DET) micelles facilitated rapid, but transient gene expression. These findings suggest that introduction of cRGD to polyplex micelles might create novel and useful functions for gene transfer and contribute to the establishment of efficient gene therapy for vascular diseases.

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The Adaptor Protein Shc Couples a Class of Integrins to the Control of Cell Cycle Progression

Cited by 711 publications

References 47 publications

Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

Signaling by integrin receptors

Impact of polyplex micelles installed with cyclic RGD peptide as ligand on gene delivery to vascular lesions

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