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Query: UNIPROT:P06889 (Mol)
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Heparin-binding growth factors (HBGFs) bind to high-affinity cell surface receptors which possess intrinsic tyrosine kinase activity. A Mr 150,000 protein phosphorylated on tyrosine in response to class 1 HBGF (HBGF-1) was purified and partially sequenced. On the basis of this sequence, cDNA clones were isolated from a human endothelial cell library and identified as encoding phospholipase C-gamma. Phosphorylation of phospholipase C-gamma in intact cells treated with HBGF-1 was directly demonstrated by using antiphospholipase C-gamma antibodies. Thus, HBGF-1 joins epidermal growth factor and platelet-derived growth factor, whose receptor activation leads to tyrosine phosphorylation and probable activation of phospholipase C-gamma.
Mol Cell Biol 1990 Sep
PMID:Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. 216 38

Overexpression of phospholipase C-gamma in fibroblasts led to increased tyrosine phosphorylation of this enzyme in response to platelet-derived growth factor and basic fibroblast growth factor. This correlated with increased phosphoinositide release but not with enhanced mitogenicity. Thus, phospholipase C-gamma-mediated phosphoinositide metabolism may not be limiting in the signaling pathways initiated by these growth factors.
Mol Cell Biol 1990 Nov
PMID:Overexpression of phospholipase C-gamma in NIH 3T3 fibroblasts results in increased phosphatidylinositol hydrolysis in response to platelet-derived growth factor and basic fibroblast growth factor. 217 91

Platelet-derived growth factor (PDGF) is a potent mitogen in human serum which specifically stimulates the proliferation of mesenchymal cells. We have now examined normal human mammary epithelial cells (HMEC) derived from reduction mammaplasties and grown in a serum-free defined medium. Medium conditioned by HMEC contained a PDGF-like activity that competed with [125I]PDGF for binding to PDGF receptors in normal human fibroblasts. When conditioned media were incubated with antiserum specific for either PDGF-A or PDGF-B, only PDGF-A antiserum was capable of inhibiting binding of conditioned media to PDGF receptors. Using an RNase protection assay, mRNA from normal HMEC was probed for both the PDGF-A and PDGF-B chains. Little or no PDGF-B was found in HMEC strains, while a strong signal was seen with the PDGF-A probe. When HMEC were grown in the presence of transforming growth factor-beta (TGF beta) for 48 h, inhibition of growth was observed in association with a 20- to 40-fold stimulation of PDGF-B mRNA and a 2-fold stimulation of PDGF-A mRNA. This mRNA induction was extremely rapid (within 1 h), and secreted PDGF activity was induced 2- to 3-fold. Two other HMEC growth inhibitors and differentiating agents, sodium butyrate and phorbol ester 12-O-tetradecanoylphorbol-13-acetate, had no effect on PDGF mRNA regulation. The current study suggests that PDGF gene induction is an extremely rapid and specific indicator of TGF beta function regardless of whether TGF beta is acting in a growth stimulatory or inhibitory manner. Any role of PDGF-B in TGF beta modulation of differentiation of normal or malignant mammary gland remains to be determined.
Mol Endocrinol 1990 Jul
PMID:Transforming growth factor-beta induces platelet-derived growth factor (PDGF) messenger RNA and PDGF secretion while inhibiting growth in normal human mammary epithelial cells. 217 25

Two platelet-derived growth factor A-chain proteins, termed short and long A chains, are generated as a result of alternative mRNA splicing of exon 6 of the A-chain gene. S1 nuclease mapping and polymerase chain reaction analyses demonstrate that both short and long A-chain transcripts are expressed in a variety of normal tissues. In addition, immunohistochemical localization of long A-chain protein reveals a cellular distribution identical to that observed with platelet-derived growth factor heteroserum.
Mol Cell Biol 1990 Nov
PMID:Alternatively spliced platelet-derived growth factor A-chain transcripts are not tumor specific but encode normal cellular proteins. 223 32

A set of immediate-early genes that are rapidly activated by serum or purified platelet-derived growth factor in mouse 3T3 fibroblasts has been previously identified. Among these genes, several are related to known or putative transcription factors and growth factors, supporting the notion that some of these genes encode regulatory molecules important to cell growth. We show here that a member of this set of genes, cyr61 (originally identified by its cDNA 3CH61), encodes a 379-amino-acid polypeptide rich in cysteine residues. cyr61 can be induced through protein kinase C-dependent and -independent pathways. Unlike many immediate-early genes that are transiently expressed, the cyr61 mRNA is accumulated from the G0/G1 transition through mid-G1. This expression pattern is due to persistent transcription, while the mRNA is rapidly turned over during the G0/G1 transition and in mid-G1 at the same rate. In logarithmically growing cells, the cyr61 mRNA level is constant throughout the cell cycle. Cyr61 contains an N-terminal secretory signal sequence; however, it is not detected in the culture medium by immunoprecipitation. Cyr61 is synthesized maximally at 1 to 2 h after serum stimulation and has a short half-life within the cell.
Mol Cell Biol 1990 Jul
PMID:Expression of cyr61, a growth factor-inducible immediate-early gene. 235 16

The understanding of biologic and pathophysiologic processes in lung is aided by a technique for ascertaining the transcriptional phenotype of small numbers of cells examined in vivo. The mRNA phenotyping procedure consists of scaled-down methods for isolating mRNA from small numbers of cells, followed by reverse transcription of the RNA and specifically primed amplification of the cDNA by the polymerase chain reaction. We show an example of the use of the technique in a study of expression of platelet-derived growth factor and other growth factor genes in macrophages isolated from wound cylinders implanted in mice. With this technique, the transcriptional phenotype of purified normal lung epithelial and mesenchymal cells, macrophages, or cells obtained from lavaged lungs or punch biopsy specimens can be examined as a rapid first step in understanding molecular processes in the lung.
Am J Respir Cell Mol Biol 1990 Jan
PMID:mRNA phenotyping for studying gene expression in small numbers of cells: platelet-derived growth factor and other growth factors in wound-derived macrophages. 240 72

Various oncogenes or epidermal growth factor (EGF) induce transcription of a 1.9-kilobase RNA (transin RNA) in rat fibroblasts. The induction by EGF can be blocked by cycloheximide. Thus the response of the transin gene to EGF appears to require de novo protein synthesis. Transin RNA induction is specific to EGF, as neither insulin, platelet-derived growth factor, fibroblast growth factor, nor transforming growth factor beta could elicit the same response. However, transforming growth factor beta could block the EGF induction of transin RNA. Whereas the calcium ionophore A23187 and the tumor promoter TPA, either alone or administered together, did not increase transin RNA levels, TPA could synergise with a serum factor to effect such an increase. Dibutyryl cyclic AMP also induced transin RNA. Treatment of cells with the microfilament-disrupting agent cytochalasin B, but not the microtubule-disrupting agent colcemid, resulted in an increase in transin RNA levels, suggesting a role for the cytoskeleton in control of transin gene expression. The transin RNA does not contain repeated sequences and appears to be encoded by a single-copy gene. The protein sequence encoded by the last four exons of the transin gene shows some homology to two regions of the heme-binding protein hemopexin.
Mol Cell Biol 1986 May
PMID:Isolation of the oncogene and epidermal growth factor-induced transin gene: complex control in rat fibroblasts. 243 Dec 84

Mast-cell-mediated mitogenesis in intact tissues is a paracrine reaction the molecular mechanisms of which still have to be elucidated. One strategy worth exploring is to study the mitogenic reaction under as defined conditions as possible. The present study demonstrates that in the virtually avascular rat mesentery, organ-cultured in a biochemically-defined medium, activation of mast cells induced a mitogenic reaction in fibroblasts and mesothelial cells, the two predominant, morphologically distinct neighboring cell types. Thus the system provides a means of studying the influence of defined molecules in the growth medium on the outcome of a mitogenic response in these two cell types in situ. It was further observed that exogenous platelet-derived growth factor (PDGF) was not essential for this mast-cell-mediated mitogenic reaction to occur in the tissue-bound fibroblasts and mesothelial cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:Molecular aspects of mast-cell-mediated mitogenesis in fibroblasts and mesothelial cells in situ. 245 40

To investigate the role of platelet-derived growth factor (PDGF) during human placental development, expression of the genes encoding PDGF, the PDGF-receptor (PDGF-R) and the c-fos protooncogene was measured. Messenger RNAs for these genes were detected throughout pregnancy and peaked coordinately during the second trimester. An identical pattern of PDGF-R protein expression was confirmed by immunoblotting using a specific PDGF-R antiserum, measurement of PDGF-R kinase activity, and [125I]PDGF binding. These findings show that the components of the PDGF pathway are expressed in a concerted fashion throughout human pregnancy and are present at especially high levels during the midtrimester. Our observations suggest that through autocrine and/or paracrine mechanisms, PDGF is likely to play an important role in placental homeostasis.
Mol Endocrinol 1988 Jul
PMID:Developmental expression of platelet-derived growth factor and its receptor in the human placenta. 245

We have carried out a comparative study of the protein tyrosine phosphorylation induced by a wide range of mitogenic stimuli on a single cell type, Swiss 3T3 mouse fibroblasts. For this purpose we have used high-affinity antibodies directed to phosphotyrosine residues on proteins (Wang: Mol. Cell. Biol. 5:3640-3643, 1985) in immunoblotting and immunofluorescence microscopy experiments. Immunoblotting experiments showed that all of the mitogens tested, including epidermal growth factor, platelet-derived growth factor, basic fibroblast growth factor, insulin, fetal calf serum, trypsin, and 12-O-tetradecanoylphorbol-13-acetate, increased the phosphorylation on tyrosine of a number of proteins. Most of the increase in tyrosine phosphorylation induced by each factor involved a small set of proteins with apparent molecular weights (Mr) above 50,000. Following stimulation with epidermal growth factor, platelet-derived growth factor, and basic fibroblast growth factor, increased phosphotyrosine modification of proteins with molecular weights corresponding to those of the respective receptors was observed. A protein band of apparent Mr 160,000 contained substantially increased levels of phosphotyrosine following insulin treatment, but tyrosine phosphorylation of the insulin receptor was apparently below the level of detectability. The phosphotyrosine content of proteins with apparent Mr of 220,000, 120,000, and 70,000 was increased by all the agents tested. Phosphorylation on tyrosine of most of the proteins increased within a few minutes of the mitogenic stimulation, reached a peak, and returned more slowly to basal levels. Immunofluorescence labeling with the antibodies specific for phosphotyrosine showed a substantial increase in the amount of phosphotyrosine containing proteins only in the presence of platelet-derived growth factor and fetal calf serum. This finding suggests that most of the proteins phosphorylated on tyrosine in Swiss 3T3 fibroblasts are not concentrated in specific subcellular structures, but rather are diffusely distributed throughout the cell and are therefore not detectable by immunofluorescence microscopy.
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PMID:Comparative study of the tyrosine phosphorylation of proteins in Swiss 3T3 fibroblasts stimulated by a variety of mitogenic agents. 245 39


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