Platelet-derived growth factor (PDGF)-AB-mediated phosphorylation of PDGF <i>β</i> receptors

Coats, Steven; Love, Harold D.; Pledger, W. J.

doi:10.1042/bj2970379

Cited by 8 publications

(5 citation statements)

References 35 publications

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“…Essentially comparable levels of Stat3 were present in PDGF b immunoprecipitates of both stimulated and unstimulated cells ( To determine if the kinase responsible for Stat3 phosphorylation in PDGF-treated cells was present in Stat3/PDGF b receptor complexes, extracts of cells treated with or without PDGF for 10 min at 378C were immunoprecipitated with antibody to the PDGF b receptor or to Tyr 705-phosphorylated Stat3; precipitated material was incubated with [g-32 P]ATP and resolved by SDS ± PAGE. In accord with our previous studies (Harrington et al, 1985;Drozdo and Pledger, 1991;Olashaw et al, 1991;Coats et al, 1994), PDGF receptor activation induced by PDGF treatment in vivo could be visualized by incubation of immune complexes with [g-32 P]ATP in vitro (Figure 4, lanes 2 and 4). In addition, in vitro PDGF-dependent phosphorylation of Stat3 was also evident, regardless of whether Stat3 was directly immunoprecipitated (along with activated PDGF receptors, lane 4) or was co-precipitated by antibody to the PDGF b receptor (lane 2; arrow indicates where Stat3 runs on gel).…”

Section: Pdgf-dependent Tyrosine Phosphorylation Of Stat3supporting

confidence: 71%

Activation of Stat3 preassembled with platelet-derived growth factor β receptors requires Src kinase activity

et al. 2000

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Members of the STAT family of transcriptional regulators modulate the expression of a variety of gene products that promote cell proliferation, survival and transformation. Although initially identi®ed as mediators of cytokine signaling, the STAT proteins are also activated by, and thus may contribute to the actions of, polypeptide growth factors. To de®ne the mechanism by which these factors activate STATs, we examined the process of Stat3 activation in Balb/c-3T3 ®broblasts treated with platelet-derived growth factor (PDGF). As STATs are activated by tyrosine phosphorylation, and as PDGF receptors are ligand-activated tyrosine kinases, we considered the possibility that Stat3 interacts with and is phosphorylated by PDGF receptors. We ®nd that Stat3 associates with PDGF b receptors in both the presence and, surprisingly, the absence of PDGF. Moreover, Stat3 was phosphorylated on tyrosine in PDGF b receptor immunoprecipitates of PDGF-treated but not untreated cells. Although required, receptor activation was insucient for Stat3 activation. When added to cells in combination with a pharmacologic agent (PD180970) that speci®cally inhibits the activity of Src family tyrosine kinases, PDGF did not activate Stat3 as monitored by electrophoretic mobility shift assay. PD180970 did not aect MAPK activation by PDGF or the JAK-dependent activation of Stat3 by interleukin-6. The necessity of Src activity for Stat3 activation by PDGF was further evidenced by data showing the presence of Src in complexes containing both Stat3 and PDGF b receptors in PDGF-treated cells. These results suggest a novel mechanism of STAT activation in which inactive Stat3 pre-assembles with inactive PDGF receptors, and in response to ligand binding and in a manner dependent on Src kinase activity, is rapidly phosphorylated and activated. Additional data demonstrate that Src kinase activity is also required for PDGF stimulation of DNA synthesis in density-arrested cells.

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Section: Pdgf-dependent Tyrosine Phosphorylation Of Stat3supporting

confidence: 71%

Activation of Stat3 preassembled with platelet-derived growth factor β receptors requires Src kinase activity

et al. 2000

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“…PDGF expression has been reported in primary cell lines or tissues of non-small cell cancer , but not, or rarely, in small-cell cancer [6,7] . Malignant PM cells predominantly express PDGF ␤ -receptors, which bind PDGF-BB [8,9] and PDGF-AB dimers [10,11] . Low expression of PDGF ␣ -receptors has been reported as well.…”

Section: Introductionmentioning

confidence: 99%

Serum PDGF-AB in Pleural Mesothelioma

Filiberti¹,

Marroni²,

Neri³

et al. 2005

Tumor Biol

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Overexpression of platelet-derived growth factor (PDGF) has been observed in lung and pleural tumors. The aim of this study was to evaluate the diagnostic and prognostic role of serum PDGF in pleural mesothelioma (PM). Four groups of subjects were studied: 93 malignant PM patients, 33 primary non small cell lung cancer patients, 51 subjects exposed to asbestos, defined as high-risk controls, and 24 healthy controls. PDGF-AB mean concentration was higher in PM patients (45.8 ng/ml) than in high-risk controls (33.1 ng/ml) and healthy controls (26.8 ng/ml). Using the cut-off level of 49.8 ng/ml, corresponding to the mean + 2SD of PDGF-AB in healthy controls, 43% of PM patients showed positive PDGF-AB levels. Survival was evaluated in 82 PM patients. At the end of the follow-up (median 9.8 months) 80.5% of patients had died. Median survival was 13.1 and 7.9 months for patients with PDGF-AB lower and higher than the cut-off, respectively. Adjusting for age, sex, histology and platelet count, positive PDGF-AB levels were associated with lower survival (OR = 1.2, 95%CI: 0.9–1.6), even if not significantly so. In conclusion, serum PDGF may represent a useful additional parameter to prognostic factors already available for PM.

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“…1 g ). Because PTM, in response to ligand stimulation, is a distinctive sign of RTK ubiquitination, which leads to internalization and down-regulation of signaling ( Coats et al, 1994 ; Mori et al, 1995 ), we next monitored the covalent attachment of endogenous or Myc-tagged ubiquitin to PDGFRα by immunoprecipitation (IP) in NIH3T3 sh IFT20 cells stimulated with PDGF-AA for 10 min in the absence or presence of Dox. The results revealed a prominent reduction in receptor polyubiquitination in IFT20-depleted cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases

Schmid

Schou

Vilhelm

et al. 2017

Journal of Cell Biology

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Platelet-derived growth factor (PDGF)-AB-mediated phosphorylation of PDGF β receptors

Cited by 8 publications

References 35 publications

Activation of Stat3 preassembled with platelet-derived growth factor β receptors requires Src kinase activity

Activation of Stat3 preassembled with platelet-derived growth factor β receptors requires Src kinase activity

Serum PDGF-AB in Pleural Mesothelioma

IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases

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