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PMID: 2165603 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Coexpression of the platelet-derived growth factor (PDGF) B chain and the PDGF beta receptor in isolated pancreatic islet cells stimulates DNA synthesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 15 ·1990-08-00 ·Pages 5807-11

Welsh M, Claesson-Welsh L, Hallberg A, Welsh N, Betsholtz C, Arkhammar P, Nilsson T, Heldin CH, Berggren PO

Abstract

Suspensions rich in pancreatic beta cells were transfected by means of electroporation or by using the liposome technique with DNA constructs coding for the B chain of platelet-derived growth factor (PDGF) and the PDGF alpha and beta receptors to induce a mitotic response in this slowly replicating cell type. Transfection with the B-chain construct induced synthesis of the PDGF B-chain homodimer (PDGF-BB) as assessed by the presence of 125I-labeled PDGF-BB competing activity in the conditioned medium of the transfected islet cells. Moreover, islet cells transfected with the PDGF beta-receptor construct exhibited increased immunofluorescence staining with a PDGF beta-receptor antibody. These cells also displayed increased 125I-labeled PDGF-BB binding compared with control transfected cells. Cotransfection with the B-chain construct or the addition of 10% fetal bovine serum or purified PDGF all induced DNA synthesis in islet cells transfected with the PDGF beta-receptor construct. Islet cells transfected with the PDGF alpha-receptor construct did not respond with stimulation of [3H]thymidine incorporation to any of the PDGF isoforms (PDGF-AA, -AB, or -BB). Cotransfection of the PDGF alpha- and beta-receptor constructs resulted in a loss of the DNA synthesis response to PDGF. The beta cells exhibited elevated levels of [3H]inositol trisphosphate after transfection with the B-chain and beta-receptor constructs, indicating activation of phospholipase C. Islet cells transfected with the different receptor constructs exhibited different patterns of tyrosine phosphorylation upon ligand activation. The results demonstrate that pancreatic islet cells can be stimulated to increase DNA synthesis by transfection with the PDGF beta-receptor gene, whereas cotransfection with the alpha-receptor gene may attenuate the growth response.

MeSH Terms
Animals Cell Line Cells, Cultured DNA Replication Fluorescent Antibody Technique Gene Library Glioma Humans Islets of Langerhans/cytology,metabolism Kinetics Macromolecular Substances Mice Plasmids Platelet-Derived Growth Factor/genetics,physiology Protein-Tyrosine Kinases/genetics Proto-Oncogene Proteins/genetics,physiology Proto-Oncogene Proteins c-sis Receptors, Cell Surface/genetics,physiology Receptors, Platelet-Derived Growth Factor Transfection
Chemicals
Macromolecular Substances Platelet-Derived Growth Factor Proto-Oncogene Proteins Proto-Oncogene Proteins c-sis Receptors, Cell Surface Protein-Tyrosine Kinases Receptors, Platelet-Derived Growth Factor
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Welsh M
Department of Medical Cell Biology, Uppsala University, Sweden.
Claesson-Welsh L
Hallberg A
Welsh N
Betsholtz C
Arkhammar P
Nilsson T
Heldin C H
Berggren P O
References (33)
33 references, click to expand
  1. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  2. Expression of three recombinant homodimeric isoforms of PDGF in Saccharomyces cerevisiae: evidence for difference in receptor binding and functional activities.
    Growth Factors. 1989;1(3):271-81 PMID: 2560933
  3. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus.
    Nature. 1983 Jul 7-13;304(5921):35-9 PMID: 6306471
  4. Structural and immunological similarities between simian sarcoma virus gene product(s) and human platelet-derived growth factor.
    Nature. 1983 Oct 13-19;305(5935):605-8 PMID: 6312326
  5. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes.
    Nature. 1983 Dec 8-14;306(5943):557-61 PMID: 6358900
  6. A glioma-derived analog to platelet-derived growth factor: demonstration of receptor competing activity and immunological crossreactivity.
    Proc Natl Acad Sci U S A. 1984 Feb;81(3):926-30 PMID: 6322178
  7. Use of an antiserum against phosphotyrosine for the identification of phosphorylated components in human fibroblasts stimulated by platelet-derived growth factor.
    J Biol Chem. 1984 Sep 10;259(17):11145-52 PMID: 6206062
  8. Purification and properties of porcine platelet-derived growth factor.
    EMBO J. 1984 Dec 1;3(12):2963-7 PMID: 6526008
  9. Nucleotide sequence of transforming human c-sis cDNA clones with homology to platelet-derived growth factor.
    Nucleic Acids Res. 1985 Jul 25;13(14):5007-18 PMID: 2991848
  10. Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis.
    Nature. 1985 Aug 22-28;316(6030):748-50 PMID: 4033772
  11. A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains.
    Nature. 1986 Feb 6-12;319(6053):511-4 PMID: 3456080
  12. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors.
    Nature. 1986 Sep 18-24;323(6085):226-32 PMID: 3020426
  13. Human melanoma cell lines of primary and metastatic origin express the genes encoding the chains of platelet-derived growth factor (PDGF) and produce a PDGF-like growth factor.
    Proc Natl Acad Sci U S A. 1986 Oct;83(19):7197-200 PMID: 3020539
  14. Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity.
    Cell. 1987 Sep 25;50(7):1021-9 PMID: 2441878
  15. Effects of platelet-derived growth factor and somatomedin-C/insulin-like growth factor I on the deoxyribonucleic acid replication of fetal rat islets of Langerhans in tissue culture.
    Endocrinology. 1988 Jan;122(1):214-8 PMID: 3275535
  16. Platelet-derived growth factor receptors expressed by cDNA transfection couple to a diverse group of cellular responses associated with cell proliferation.
    J Biol Chem. 1988 Jan 25;263(3):1482-7 PMID: 2826480
  17. Stimulation of pancreatic islet beta-cell replication by oncogenes.
    Proc Natl Acad Sci U S A. 1988 Jan;85(1):116-20 PMID: 2829167
  18. Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: evidence for more than one receptor class.
    Proc Natl Acad Sci U S A. 1988 May;85(10):3435-9 PMID: 2835772
  19. Two classes of PDGF receptor recognize different isoforms of PDGF.
    Science. 1988 Jun 10;240(4858):1529-31 PMID: 2836952
  20. Characterization of two monoclonal antibodies reactive with the external domain of the platelet-derived growth factor receptor.
    J Biol Chem. 1988 Jul 25;263(21):10429-35 PMID: 2455716
  21. Binding of different dimeric forms of PDGF to human fibroblasts: evidence for two separate receptor types.
    EMBO J. 1988 May;7(5):1387-93 PMID: 2842148
  22. A human glioma cell line secretes three structurally and functionally different dimeric forms of platelet-derived growth factor.
    Eur J Biochem. 1988 Sep 1;176(1):179-86 PMID: 2458254
  23. Expression of functional human EGF receptor on murine bone marrow cells.
    EMBO J. 1988 Sep;7(9):2749-56 PMID: 3053164
  24. Signal transduction from membrane to cytoplasm: growth factors and membrane-bound oncogene products increase Raf-1 phosphorylation and associated protein kinase activity.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8855-9 PMID: 3057494
  25. Different effects of homo- and heterodimers of platelet-derived growth factor A and B chains on human and mouse fibroblasts.
    EMBO J. 1988 Dec 1;7(12):3727-35 PMID: 2463166
  26. cDNA cloning and expression of a human platelet-derived growth factor (PDGF) receptor specific for B-chain-containing PDGF molecules.
    Mol Cell Biol. 1988 Aug;8(8):3476-86 PMID: 2850496
  27. Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes.
    Science. 1989 Feb 10;243(4892):800-4 PMID: 2536956
  28. Role of tyrosine kinase and membrane-spanning domains in signal transduction by the platelet-derived growth factor receptor.
    Mol Cell Biol. 1988 Dec;8(12):5126-31 PMID: 2854192
  29. Transfection of insulin-producing cells with a transforming c-Ha-ras oncogene stimulates phospholipase C activity.
    Biochem J. 1989 May 1;259(3):701-7 PMID: 2658977
  30. cDNA cloning and expression of the human A-type platelet-derived growth factor (PDGF) receptor establishes structural similarity to the B-type PDGF receptor.
    Proc Natl Acad Sci U S A. 1989 Jul;86(13):4917-21 PMID: 2544881
  31. PDGF A chain homodimers drive proliferation of bipotential (O-2A) glial progenitor cells in the developing rat optic nerve.
    EMBO J. 1989 Apr;8(4):1049-56 PMID: 2545439
  32. Platelet-derived growth factor induces rapid and sustained tyrosine phosphorylation of phospholipase C-gamma in quiescent BALB/c 3T3 cells.
    Mol Cell Biol. 1989 Jul;9(7):2934-43 PMID: 2550789
  33. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor.
    Science. 1983 Jul 15;221(4607):275-7 PMID: 6304883
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.15.5807
Published
1990-08-00
Pages
5807-11
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC54417
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.87.15.5807 PMC Full Text View journal details
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