Platelet-derived growth factor. II. Specific binding to cultured cells.

Cantilever with modified aptamers on the gold surface was employed to detect platelet-derived growth factor-BB (PDGF-BB) and cocaine. The deflection increased when PDGF-BB and cocaine were added into the flowing cell, respectively. The defection depended on the concentration of PDGF-BB and cocaine. It was also found the microcantiver went back to the same position as without cocaine after adding cocaine aptamer in situ, which proved that the cantilever could be reused. The deflection arose from the specific interaction between aptamer and its target.

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Human platelet-derived growth factor: radioimmunoassay and discovery of a specific plasma-binding protein.

The Journal of Cell Biology ◽

10.1083/jcb.97.2.383 ◽

1983 ◽

Vol 97 (2) ◽

pp. 383-388 ◽

Cited By ~ 61

Author(s):

J S Huang ◽

S S Huang ◽

T F Deuel

Keyword(s):

Growth Factor ◽

Human Plasma ◽

Wound Repair ◽

Cultured Cells ◽

Binding Protein ◽

Biological Fluids ◽

Platelet Derived Growth Factor ◽

Plasma Binding ◽

Platelet Factor ◽

Immunodiffusion Analysis

The platelet-derived growth factor (PDGF) is the principal mitogen in serum for cultured cells of mesenchymal origin. PDGF also is a potent chemotactic protein for inflammatory cells and for cells required for wound repair. Because activity levels of PDGF in biological fluids are difficult to measure, we attempted to develop a radioimmunoassay for PDGF. Rabbits were immunized with purified PDGF; the antiserum obtained was monospecific for PDGF in immunodiffusion analysis against concentrated platelet lysates, serum, and plasma. A radioimmunoassay for PDGF was developed with a sensitivity of congruent to 0.2 ng/ml. Levels of PDGF in plasma/serum were measured and compared with PDGF levels determined by a receptor-competition assay and by a standard biological assay measuring incorporation of [3H]thymidine into 3T3 cells. Radioimmunoassay showed apparent PDGF levels of 50 ng/ml in human plasma and 103 ng/ml in serum. The 50 ng/ml PDGF in plasma was unexpected because the plasma samples contained little or no platelet release products as determined by very low levels of platelet factor 4. We therefore sought an immunologically reactive PDGF molecule in human plasma. No immunologically reactive protein was detected by immunodiffusion analysis or when plasma was treated with an immunoaffinity gel. Subsequently, a 125I-PDGF-binding protein was identified; the 125I-PDGF-plasma-binding protein complex was not reactive with anti-PDGF immunoglobulin. Correction for 125I-PDGF bound by the plasma-binding protein established serum levels of PDGF of congruent to 50 ng/ml; congruent to 50 ng/ml PDGF was found in serum by radioreceptor-competition assays and by mitogenic assays as well. The plasma-binding protein may serve to clear PDGF released in the circulation, thereby limiting PDGF activity to its local interactions at the site of blood-vessel injury.

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Platelet-derived growth factor is a principal inductive factor modulating mannose 6-phosphate/insulin-like growth factor-II receptor gene expression via a distal E-box in activated hepatic stellate cells

Biochemical Journal ◽

10.1042/0264-6021:3450225 ◽

2000 ◽

Vol 345 (2) ◽

pp. 225 ◽

Cited By ~ 3

Author(s):

Joel A. WEINER ◽

Anping CHEN ◽

Bernard H. DAVIS

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Hepatic Stellate Cells ◽

Receptor Gene ◽

Stellate Cells ◽

Platelet Derived Growth Factor ◽

Insulin Like Growth Factor ◽

Factor Ii ◽

E Box ◽

Receptor Gene Expression

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Multiple Effects of Human Platelet-Derived Growth Factor (PDGF) on Arachidonic Acid and Prostaglandin Metabolism in Cultured Cells

Progress in Applied Microcirculation - Microcirculation and Inflammation: Vessel Wall - Inflammatory Cells - Mediator Interaction ◽

10.1159/000414442 ◽

2015 ◽

pp. 143-151

Author(s):

A. J. R. Habenicht ◽

M. Goerig ◽

W. Zeh ◽

P. Salbach ◽

D. Rothe ◽

...

Keyword(s):

Arachidonic Acid ◽

Growth Factor ◽

Cultured Cells ◽

Human Platelet ◽

Platelet Derived Growth Factor ◽

Prostaglandin Metabolism

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Insulin Receptor Isoform A, a Newly Recognized, High-Affinity Insulin-Like Growth Factor II Receptor in Fetal and Cancer Cells

Molecular and Cellular Biology ◽

10.1128/mcb.19.5.3278 ◽

1999 ◽

Vol 19 (5) ◽

pp. 3278-3288 ◽

Cited By ~ 572

Author(s):

F. Frasca ◽

G. Pandini ◽

P. Scalia ◽

L. Sciacca ◽

R. Mineo ◽

...

Keyword(s):

Growth Factor ◽

Insulin Receptor ◽

Cancer Biology ◽

Cultured Cells ◽

Biological Effects ◽

Metabolic Effects ◽

Insulin Like Growth Factor ◽

Factor Ii ◽

Fetal Fibroblasts ◽

Igf I

ABSTRACT Insulin-like growth factor II (IGF-II) is a peptide growth factor that is homologous to both insulin-like growth factor I (IGF-I) and insulin and plays an important role in embryonic development and carcinogenesis. IGF-II is believed to mediate its cellular signaling via the transmembrane tyrosine kinase type 1 insulin-like growth factor receptor (IGF-I-R), which is also the receptor for IGF-I. Earlier studies with both cultured cells and transgenic mice, however, have suggested that in the embryo the insulin receptor (IR) may also be a receptor for IGF-II. In most cells and tissues, IR binds IGF-II with relatively low affinity. The IR is expressed in two isoforms (IR-A and IR-B) differing by 12 amino acids due to the alternative splicing of exon 11. In the present study we found that IR-A but not IR-B bound IGF-II with an affinity close to that of insulin. Moreover, IGF-II bound to IR-A with an affinity equal to that of IGF-II binding to the IGF-I-R. Activation of IR-A by insulin led primarily to metabolic effects, whereas activation of IR-A by IGF-II led primarily to mitogenic effects. These differences in the biological effects of IR-A when activated by either IGF-II or insulin were associated with differential recruitment and activation of intracellular substrates. IR-A was preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney and had a relatively increased proportion of isoform A. IR-A expression was also increased in several tumors including those of the breast and colon. These data indicate, therefore, that there are two receptors for IGF-II, both IGF-I-R and IR-A. Further, they suggest that interaction of IGF-II with IR-A may play a role both in fetal growth and cancer biology.

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PLATELET-DERIVED GROWTH FACTOR IS A CHEMOATTRACTANT FOR CULTURED CELLS

Cellular Responses to Molecular Modulators ◽

10.1016/b978-0-12-509380-4.50050-8 ◽

1981 ◽

pp. 515 ◽

Cited By ~ 1

Author(s):

G.R. Grotendorst ◽

T. Chang ◽

H.E.J. Seppä ◽

S. Seppä ◽

E. Schiffmann ◽

...

Keyword(s):

Growth Factor ◽

Cultured Cells ◽

Platelet Derived Growth Factor

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Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor

Molecular and Cellular Biology ◽

10.1128/mcb.13.11.6889-6896.1993 ◽

1993 ◽

Vol 13 (11) ◽

pp. 6889-6896

Author(s):

R Nishimura ◽

W Li ◽

A Kashishian ◽

A Mondino ◽

M Zhou ◽

...

Keyword(s):

Growth Factor ◽

Binding Site ◽

Specific Binding ◽

Growth Factor Receptors ◽

Signaling Molecules ◽

Sh2 Domain ◽

Platelet Derived Growth Factor ◽

Pdgf Receptor ◽

Intact Cells ◽

Sh2 Domains

Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.

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Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

Molecular and Cellular Biology ◽

10.1128/mcb.13.11.6889 ◽

1993 ◽

Vol 13 (11) ◽

pp. 6889-6896 ◽

Cited By ~ 118

Author(s):

R Nishimura ◽

W Li ◽

A Kashishian ◽

A Mondino ◽

M Zhou ◽

...

Keyword(s):

Growth Factor ◽

Binding Site ◽

Specific Binding ◽

Growth Factor Receptors ◽

Signaling Molecules ◽

Sh2 Domain ◽

Platelet Derived Growth Factor ◽

Pdgf Receptor ◽

Intact Cells ◽

Sh2 Domains

Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.

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In vitro modeling of glioblastoma initiation using PDGF-AA and p53-null neural progenitors

Neuro-Oncology ◽

10.1093/neuonc/noaa093 ◽

2020 ◽

Vol 22 (8) ◽

pp. 1150-1161 ◽

Cited By ~ 1

Author(s):

Alexandra K Bohm ◽

Jessica DePetro ◽

Carmen E Binding ◽

Amanda Gerber ◽

Nicholas Chahley ◽

...

Keyword(s):

Growth Factor ◽

Genome Stability ◽

Cultured Cells ◽

Growth Factor Receptor ◽

Platelet Derived Growth Factor ◽

Early Event ◽

Wild Type ◽

Microscopic Appearance ◽

Human Gbm

Abstract Background Imagining ways to prevent or treat glioblastoma (GBM) has been hindered by a lack of understanding of its pathogenesis. Although overexpression of platelet derived growth factor with two A-chains (PDGF-AA) may be an early event, critical details of the core biology of GBM are lacking. For example, existing PDGF-driven models replicate its microscopic appearance, but not its genomic architecture. Here we report a model that overcomes this barrier to authenticity. Methods Using a method developed to establish neural stem cell cultures, we investigated the effects of PDGF-AA on subventricular zone (SVZ) cells, one of the putative cells of origin of GBM. We microdissected SVZ tissue from p53-null and wild-type adult mice, cultured cells in media supplemented with PDGF-AA, and assessed cell viability, proliferation, genome stability, and tumorigenicity. Results Counterintuitive to its canonical role as a growth factor, we observed abrupt and massive cell death in PDGF-AA: wild-type cells did not survive, whereas a small fraction of null cells evaded apoptosis. Surviving null cells displayed attenuated proliferation accompanied by whole chromosome gains and losses. After approximately 100 days in PDGF-AA, cells suddenly proliferated rapidly, acquired growth factor independence, and became tumorigenic in immune-competent mice. Transformed cells had an oligodendrocyte precursor-like lineage marker profile, were resistant to platelet derived growth factor receptor alpha inhibition, and harbored highly abnormal karyotypes similar to human GBM. Conclusion This model associates genome instability in neural progenitor cells with chronic exposure to PDGF-AA and is the first to approximate the genomic landscape of human GBM and the first in which the earliest phases of the disease can be studied directly.

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