Impaired Shc, Ras, and MAPK Activation but Normal Akt Activation in FL5.12 Cells Expressing an Insulin-like Growth Factor I Receptor Mutated at Tyrosines 1250 and 1251

Leahy, Madeline; Lyons, Alan M.; Krause, Darren; O’Connor, Rosemary

doi:10.1074/jbc.m309234200

Cited by 26 publications

(24 citation statements)

References 59 publications

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“…In FL5.12 lymphocytic cells expressing the Y1250F/Y1251F mutant, we found that IGF-I-mediated phosphorylation of Shc on tyrosine 313 (317 in human Shc), Ras activity, and activation of the Erk, c-Jun N-terminal kinase, and p38 pathways are all deficient (26). In this study IGF-Imediated Erk phosphorylation did not correlate with Shc phosphorylation and was also observed in Y1250F/Y1251F-expressing RϪ cells.…”

Section: Akt Activity Is Enhanced and Activation Of P38 Mapk Is Reducmentioning

confidence: 59%

“…The observation that RACK1 does not associate with the IGF-IR in FL5.12 cells and that the Y1250F/Y1251F mutant in these cells is also deficient in promoting Shc phosphorylation (26) suggests that association of RACK1 with the IGF-IR and Shc phosphorylation are two distinct phenotypes of this mutant. This observation also reveals a difference in the signals that are necessary for IGF-I-mediated Shc phosphorylation in hemopoietic cells and in adherent cells.…”

Section: Akt Activity Is Enhanced and Activation Of P38 Mapk Is Reducmentioning

confidence: 93%

“…Recently, we demonstrated that when this mutant is expressed in FL5.12 lymphocytic cells, IGF-I-mediated phosphorylation of Shc, Ras activation, and MAPK activation are all decreased (26). These findings suggest that IGF-I-mediated activation of the Shc, Ras, and MAPK pathways have a particular role in the transforming and migratory functions of the IGF-IR.…”

mentioning

confidence: 91%

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RACK1-mediated Integration of Adhesion and Insulin-like Growth Factor I (IGF-I) Signaling and Cell Migration Are Defective in Cells Expressing an IGF-I Receptor Mutated at Tyrosines 1250 and 1251

Kiely

Leahy

O׳Gorman

et al. 2005

Journal of Biological Chemistry

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102

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Section: Akt Activity Is Enhanced and Activation Of P38 Mapk Is Reducmentioning

confidence: 59%

Section: Akt Activity Is Enhanced and Activation Of P38 Mapk Is Reducmentioning

confidence: 93%

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RACK1-mediated Integration of Adhesion and Insulin-like Growth Factor I (IGF-I) Signaling and Cell Migration Are Defective in Cells Expressing an IGF-I Receptor Mutated at Tyrosines 1250 and 1251

Kiely

Leahy

O׳Gorman

et al. 2005

Journal of Biological Chemistry

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102

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“…21 Although no direct evidence has been reported for the phosphorylation of Y1280 and Y1281, several functional studies have demonstrated their importance in activating the mitogenactivated protein kinase (MAPK) signaling cascade and in suppressing apoptosis in lymphocytic cells. 30,31 We therefore designated these sites as 'physiological'. A summary of our designations is provided in Fig.…”

Section: Physiological and Nonphysiological Sites Of Tyrosine Phosphomentioning

confidence: 99%

A quantitative study of the recruitment potential of all intracellular tyrosine residues on EGFR, FGFR1 and IGF1R

et al. 2008

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Receptor tyrosine kinases transmit and process extracellular cues by recruiting intracellular signaling proteins to sites of tyrosine phosphorylation. Using protein microarrays comprising virtually every human SH2 and PTB domain, we generated quantitative protein interaction maps for three wellstudied receptors-EGFR, FGFR1 and IGF1R-using phosphopeptides derived from every intracellular tyrosine residue on each receptor, regardless of whether or not they are phosphorylated in vivo. We found that, in general, peptides derived from physiological sites of tyrosine phosphorylation bind to substantially more SH2 or PTB domains than do peptides derived from nonphysiological sites, supporting the idea that kinases and interaction domains co-evolve and suggesting that new sites arise predominantly through selection favoring advantageous interactions, rather than through selection disfavoring unwanted interactions. We also found substantial qualitative overlap in the recruitment profiles of these three receptors, suggesting that their different biological effects arise, at least in part, from quantitative differences in their affinities for the proteins they recruit.

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“…It has been reported as increased in prostate cancer, colorectal cancer and lung cancer (14,15), and also provides a mitogenic signal that acts as a growth factor for many types of tissue culture cells. IGF1 associates with tyrosine kinase receptors, such as Shc, Grb2 and Sos-1, to activate Ras and the MAPK cascade (16). Is synthesized during early fetal life, with high concentrations being found in the lung, stimulating lung growth (17).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of matrix metalloproteinase 9 and tubulin-α in pulmonary sclerosing hemangioma

Cho

Jin²,

Kim

et al. 2007

Oncol Rep

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Abstract. Pulmonary sclerosing hemangioma (PSH) is relatively rare and is usually considered a benign tumor because of its slow growth and solitary characteristics. However, several cases with lymph node metastasis have been reported, and its pathogenesis has not been fully elucidated. Three sets of PSH specimens from the Korea Lung Tissue Bank, obtained with IRB approval, were analyzed through the construction of an oligo-microarray that contained about 32,000 genes. The resulting data were confirmed by real-time RT-PCR. Protein expression levels were checked by performing immunohistochemistry (IHC) and immunoblot analysis. In the 3 specimens of PSH tissues, 72 of the 32,000 genes were commonly found up-regulated and 290 were commonly found down-regulated as compared to non-tumor tissues from each patient. Paraffin-embedded tissues from 11 cases were used to confirm the expression of matrix metalloproteinase 9 (MMP-9) and tubulin-α proteins in the non-tumor and PSH tissues via IHC. In addition, the upregulation of protein expression was confirmed by immunoblot analysis. As expected, in all cases MMP-9 and tubulin-α were expressed at significantly higher levels in the PSH than in the non-tumor tissues. This is the first report on a study of the whole genome of PSH. Increased expression of MMP-9 could induce the metastatic ability of PSH and tubulin-α might be responsible for the sclerotic character of this disease. The results of this study will be useful in helping to understand and effectively manage patients suffering from PSH.

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Impaired Shc, Ras, and MAPK Activation but Normal Akt Activation in FL5.12 Cells Expressing an Insulin-like Growth Factor I Receptor Mutated at Tyrosines 1250 and 1251

Cited by 26 publications

References 59 publications

RACK1-mediated Integration of Adhesion and Insulin-like Growth Factor I (IGF-I) Signaling and Cell Migration Are Defective in Cells Expressing an IGF-I Receptor Mutated at Tyrosines 1250 and 1251

RACK1-mediated Integration of Adhesion and Insulin-like Growth Factor I (IGF-I) Signaling and Cell Migration Are Defective in Cells Expressing an IGF-I Receptor Mutated at Tyrosines 1250 and 1251

A quantitative study of the recruitment potential of all intracellular tyrosine residues on EGFR, FGFR1 and IGF1R

Increased expression of matrix metalloproteinase 9 and tubulin-α in pulmonary sclerosing hemangioma

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