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1.
Two classes of PDGF receptor recognize different isoforms of PDGF 总被引：75，自引：0，他引：75
C E Hart J W Forstrom J D Kelly R A Seifert R A Smith R Ross M J Murray D F Bowen-Pope 《Science (New York, N.Y.)》1988,240(4858):1529-1531
Previous studies involving platelet-derived growth factor (PDGF) have been based on the premise that a single cell-surface receptor binds all three isoforms of PDGF (AA, BB, and AB). It is now shown that two populations of PDGF receptor exist and can be distinguished by their ligand binding specificity. The B receptor binds only the BB dimer, whereas the A/B receptor binds AA, BB, and AB dimers. Human dermal fibroblasts appear to express seven times as much B receptor as A/B receptor. The B receptor is responsible for most PDGF receptor phosphorylation. 相似文献
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3.
Role of phosphatidylinositol kinase in PDGF receptor signal transduction 总被引：93，自引：0，他引：93
The molecules with which the platelet-derived growth factor (PDGF) receptor interacts to elicit the biochemical reactions responsible for cell proliferation have not been identified. Antisera directed against specific PDGF receptor peptides coprecipitated a phosphatidylinositol (PI) kinase and the PDGF receptor. Immunoprecipitates from PDGF-stimulated cells contained 10 to 50 times as much PI kinase as those from unstimulated cells. Mutation of the PDGF receptor by deletion of its kinase insert region resulted in a receptor markedly less effective than the wild type in eliciting cell proliferation and defective in PDGF-stimulated PI kinase, but still capable of PDGF-induced receptor autophosphorylation and phosphoinositide hydrolysis. These data show that the PDGF receptor is physically associated with a PDGF-sensitive PI kinase that is distinct from tyrosine kinase and is not required for PDGF-induced PI hydrolysis. The finding that the mutant PDGF receptor missing the kinase insert domain elicited known early biochemical responses to PDGF, but did not associate with or regulate PI kinase, suggests a novel role for the receptor-associated PI kinase in the transmission of mitogenic signals. 相似文献
4.
Inhibition of PDGF beta receptor signal transduction by coexpression of a truncated receptor. 总被引：18，自引：0，他引：18
A mutated form of the platelet-derived growth factor (PDGF) beta receptor lacking most of its cytoplasmic domain was tested for its ability to block wild-type PDGF receptor function. PDGF induced the formation of complexes consisting of wild-type and truncated receptors. Such complexes were defective in autophosphorylation. When truncated receptors were expressed in excess compared to wild-type receptors, stimulation by PDGF of receptor autophosphorylation, association of phosphatidylinositol-3 kinase with the receptor, and calcium mobilization were blocked. Thus, a truncated receptor can inactivate wild-type receptor function by forming ligand-dependent receptor complexes (probably heterodimers) that are incapable of mediating the early steps of signal transduction. 相似文献
5.
Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes 总被引：82，自引：0，他引：82
T Matsui M Heidaran T Miki N Popescu W La Rochelle M Kraus J Pierce S Aaronson 《Science (New York, N.Y.)》1989,243(4892):800-804
6.
Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains 总被引：18，自引：0，他引：18
M P Beckmann C Betsholtz C H Heldin B Westermark E Di Marco P P Di Fiore K C Robbins S A Aaronson 《Science (New York, N.Y.)》1988,241(4871):1346-1349
Human platelet-derived growth factor (PDGF) consists of two distinct but related polypeptide chains designated PDGF-A and PDGF-B. The gene encoding PDGF-B has given rise to the v-sis oncogene. In the present study the transforming activities of PDGF-A and PDGF-B genes are compared. The PDGF-A chain gene is markedly less efficient in inducing transformation than the PDGF-B gene under the influence of the same promoter. There are significant differences in the secretory and growth stimulating properties of the two chains. These properties appear to account for the much more potent transforming ability of the PDGF-B gene. These findings provide insights into biologic properties of a growth factor responsible for potent autocrine stimulation of abnormal cell proliferation. 相似文献
7.
J A Escobedo S Navankasatussas L S Cousens S R Coughlin G I Bell L T Williams 《Science (New York, N.Y.)》1988,240(4858):1532-1534
The human platelet-derived growth factor (PDGF) receptor complementary DNA was cloned and expressed by transfection of Chinese hamster ovary (CHO) fibroblasts. The ability of CHO cells expressing the human receptor complementary DNA (CHO-HR5) to interact with different recombinant forms of PDGF (AA and BB homodimers) was tested. Both forms of PDGF bind to the transfected receptor, stimulate the receptor tyrosine kinase activity, and elicit a mitogenic response in a manner that was indistinguishable from the responses of Balb/c 3T3 cells to AA and BB forms of PDGF can be attributed to a single type of receptor and show that the AA form, like the BB form, is a true mitogen. 相似文献
8.
Vascular permeability factor, an endothelial cell mitogen related to PDGF 总被引：159，自引：0，他引：159
P J Keck S D Hauser G Krivi K Sanzo T Warren J Feder D T Connolly 《Science (New York, N.Y.)》1989,246(4935):1309-1312
Vascular permeability factor (VPF) is a 40-kilodalton disulfide-linked dimeric glycoprotein that is active in increasing blood vessel permeability, endothelial cell growth, and angiogenesis. These properties suggest that the expression of VPF by tumor cells could contribute to the increased neovascularization and vessel permeability that are associated with tumor vasculature. The cDNA sequence of VPF from human U937 cells was shown to code for a 189-amino acid polypeptide that is similar in structure to the B chain of platelet-derived growth factor (PDGF-B) and other PDGF-B-related proteins. The overall identity with PDGF-B is 18%. However, all eight of the cysteines in PDGF-B were found to be conserved in human VPF, an indication that the folding of the two proteins is probably similar. Clusters of basic amino acids in the COOH-terminal halves of human VPF and PDGF-B are also prevalent. Thus, VPF appears to be related to the PDGF/v-sis family of proteins. 相似文献
9.
Evidence that the v-sis gene product transforms by interaction with the receptor for platelet-derived growth factor 总被引：14，自引：0，他引：14
A scheme for partial purification of biologically active v-sis-coded protein from cells transformed with simian sarcoma virus (SSV) has made possible a functional comparison of the transforming protein with platelet-derived growth factor (PDGF). The SSV-transforming gene product is capable of specifically binding PDGF receptors, stimulating tyrosine phosphorylation of PDGF receptors, and inducing DNA synthesis in quiescent fibroblasts. Each of these activities was specifically inhibited by antibodies to different regions of the v-sis gene product. Moreover, viral infection of a variety of cell types revealed a strict correlation between those cells possessing PDGF receptors and those susceptible to transformation by SSV. These findings provide evidence that SSV-transforming activity is mediated by the interaction of a virus-coded mitogen with PDGF receptors. 相似文献
10.
Autocrine activation of platelet-derived growth factor (PDGF) receptors is the mechanism of transformation by the v-sis oncogene. Since the addition of PDGF does not transform normal cells, autocrine mechanisms may involve unique pathways of receptor activation. In this study autocrine stimulation of the PDGF receptor was observed in v-sis-transformed normal rat kidney (NRK) cells. In contrast to receptor activation in normal cells, autocrine activation of PDGF receptors in v-sis-transformed cells occurred in intracellular compartments, disrupting receptor processing and diverting receptors and their precursors to a chloroquine-sensitive degradation pathway. These findings show that intracellular activation of receptors by autocrine mechanisms may play a role in cell transformation. 相似文献
11.
The role of individual cysteine residues in the structure and function of the v-sis gene product 总被引：12，自引：0，他引：12
The v-sis oncogene encodes a platelet-derived growth factor (PDGF)-related product whose transforming activity is mediated by its functional interaction with the PDGF receptor. PDGF, as well as processed forms of the v-sis gene product, is a disulfide-linked dimer with eight conserved cysteine residues in the minimum region necessary for biologic activity. Site-directed mutagenesis of the v-sis gene revealed that each conserved cysteine residue was required directly or indirectly for disulfide-linked dimer formation. However, substitution of serine for cysteine codons at any of four positions had no detrimental effect on transforming activity of the encoded v-sis protein. These results establish that interchain disulfide bonds are not essential in order for this protein to act as a functional ligand for the PDGF receptor. The remaining four substitutions of serine for cysteine each inactivated transforming function of the molecule. In each case this was associated with loss of a conformation shown to involve intramolecular disulfide bonds. These studies provide insight into the role of individual cysteine residues in determining the structure of the sis/PDGF molecule critical for biological activity. 相似文献
12.
Binding of GAP to activated PDGF receptors 总被引：93，自引：0，他引：93
The ras proto-oncogene products appear to relay intracellular signals via the Ras guanosine triphosphatase (GTPase) activator protein, GAP. In dog epithelial cells expressing human platelet-derived growth factor (PDGF) receptors, binding of PDGF caused approximately one-tenth of the total GAP molecules to complex with the receptor. Studies with mutant PDGF receptors showed that maximum association required both receptor kinase activity and phosphorylatable tyrosine residues at both the identified sites of receptor autophosphorylation. 相似文献
13.
E A Bauer N Silverman D F Busiek A Kronberger T F Deuel 《Science (New York, N.Y.)》1986,234(4781):1240-1243
Patients with Werner's syndrome, an autosomal recessive disorder, undergo an accelerated aging process that leads to premature death. Fibroblasts from such patients typically grow poorly in culture. Here it is shown that fibroblasts from a patient with Werner's syndrome have a markedly attenuated mitogenic response to platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF). In contrast, they have a full mitogenic response to fetal bovine serum. Both PDGF binding and receptor numbers per cell are unaltered. The Werner's syndrome cells express high constitutive levels of collagenase in vitro. Although PDGF enhances collagenase expression through increased levels of hybridizable collagenase messenger RNA in normal skin fibroblasts, no induction of collagenase occurs in the Werner's syndrome fibroblasts. Moreover, the failure to respond to this agonist effect of PDGF is not restored by fetal bovine serum. The data suggest that failure of one or more PDGF-mediated pathways in Werner's syndrome cells may contribute to the phenotypic expression of the disorder. 相似文献
14.
Growth and transparency in the lens, an epithelial tissue, stimulated by pulses of PDGF 总被引：7，自引：0，他引：7
The rat lens undergoes dramatic growth during early postnatal development. Lens weight increased by a factor of 23 in 26 days. Growth rate per day oscillated between 0 and 87 percent. A new culture system was designed to study the oscillations in growth during development. Lens growth and transparency in vitro required pulsatile delivery of platelet-derived growth factor (PDGF) in HL-1 serum-free medium. Continuous delivery of HL-1 medium with PDGF or pulsatile delivery of HL-1 medium without PDGF resulted in lens opacity and no growth. These results provide direct evidence that PDGF stimulates an epithelial tissue and that oscillations in growth occur during normal development of the rat lens. 相似文献
15.
为探讨血小板衍生生长因子(Platelet-derived growth factor,PDGF)及其受体(PDGFR)mRNA在鹅等级前卵泡中的表达差异及生物学意义。选取健康的产蛋前期和产蛋期籽鹅各3只为试验材料,利用实时荧光定量PCR方法检测PDGF和PDGFR mRNA在产蛋前期和产蛋期鹅等级前卵泡(分为SYF、LWF、MWF、SWF、PE 5个等级)中的表达差异。结果表明:产蛋期PDGF及其受体mRNA在5个等级前卵泡中的表达量均高于产蛋前期(P0.05),说明PDGF及其受体mRNA对卵泡发育有促进作用;产蛋前期和产蛋期PDGF及其受体mRNA表达量均在初级卵泡(PE)中最高,说明初级卵泡是主要表达部位,其中颗粒细胞形态由扁平变成立方形后开始大量增殖,通过促进颗粒细胞的增殖进而促进卵泡发育;在初级卵泡向小白卵泡(SWF)发育过程中,PDGF及其受体mRNA表达量有明显下降(P0.05),推测这可能与PDGF抑制类固醇的合成进而抑制卵泡发育有关,使优势卵泡更有序的进行筛选。 相似文献
16.
Human platelet-derived growth factor (PDGF) obtained from outdated human platelets was subjected to amino-terminal amino acid sequence analysis by automated Edman degradation. Despite the apparent presence of limited proteolytic degradation of the protein derived from this method, the sequence analysis reveals two primary peptide sequences and suggests that active PDGF is composed of two, possibly homologous, peptides linked by a disulfide bond or bonds. 相似文献
17.
Addition of mouse interferon-alpha/beta (IFN) to confluent, quiescent BALB/c 3T3 (clone A31) mouse fibroblasts resulted in a block or delay in serum-induced activation of the cell cycle. It was necessary to add IFN within 6 hours after serum stimulation to inhibit nuclear labeling with [3H]thymidine. This is consistent with the time required for platelet-derived growth factor (PDGF) to induce cells to become competent to respond to additional growth factors present in platelet-poor plasma. Simultaneous addition of IFN with PDGF inhibited the PDGF-induced synthesis of a 29-kilodalton and a 35-kilodalton protein that normally occurs within 1 hour after PDGF addition. IFN also suppressed the general increase in protein synthesis that occurs by the fifth hour after PDGF addition. These results show that IFN antagonizes the action of PDGF, thereby interfering with the activation of Go cells for G1 traverse and S-phase entry. 相似文献
18.
Detection of c-sis transcripts and synthesis of PDGF-like proteins by human osteosarcoma cells 总被引：17，自引：0，他引：17
D T Graves A J Owen R K Barth P Tempst A Winoto L Fors L E Hood H N Antoniades 《Science (New York, N.Y.)》1984,226(4677):972-974
19.
Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's 总被引：101，自引：0，他引：101
M Hatakeyama M Tsudo S Minamoto T Kono T Doi T Miyata M Miyasaka T Taniguchi 《Science (New York, N.Y.)》1989,244(4904):551-556
Interleukin-2 (IL-2) binds to two distinct receptor molecules, the IL-2 receptor alpha (IL-2R alpha, p55) chain and the newly identified IL-2 receptor beta (IL-2R beta, p70-75) chain. The cDNA encoding the human IL-2R beta chain has now been isolated. The overall primary structure of the IL-2R beta chain shows no apparent homology to other known receptors. Unlike the IL-2R alpha chain, the IL-2R beta chain has a large cytoplasmic region in which a functional domain (or domains) mediating an intracellular signal transduction pathway (or pathways) may be embodied. The cDNA-encoded beta chain binds and internalizes IL-2 when expressed on T lymphoid cells but not fibroblast cells. Furthermore, the cDNA gives rise to the generation of high-affinity IL-2 receptor when co-expressed with the IL-2R alpha chain cDNA. 相似文献
20.
Expression of a platelet-derived growth factor-like protein in simian sarcoma virus transformed cells 总被引：48，自引：0，他引：48
T F Deuel J S Huang S S Huang P Stroobant M D Waterfield 《Science (New York, N.Y.)》1983,221(4618):1348-1350
The near identity of the partial amino acid sequence of human platelet-derived growth factor (PDGF) and that predicted for p28sis, the putative transforming protein of the simian sarcoma virus (SSV), suggests expression of a growth factor activity may be central for transformation by SSV. It is now reported that SSV-transformed cells but not control cells contain a growth factor activity that is identical to PDGF in immunoassay, in mitogenic dose response, and in specific mitogenic activity. The protein immunoprecipitated by antiserum to human PDGF has an apparent molecular weight of 20,000, identical to that of p20sis, the putative intracellular degradation product of p28sis. The results support the concept that expression of a PDGF-like molecule, which appears to be the product of the viral-sis gene, is responsible for the abnormal regulation of growth is SSV-transformed cells. 相似文献