Recent Developments in the Structure, Function and Regulation of Platelet-derived Growth Factor and Its Receptors

Overview

Journal Cytotechnology

Specialties Biotechnology
Genetics

Date 2012 Feb 24

PMID 22358873

Authors

J Tiesman

A Rizzino

Affiliations

Soon will be listed here.

Abstract

Recent evidence strongly suggests that production of platelet-derived growth factor (PDGF) is regulated by several mechanisms, including noncoordinate expression of the PDGF A- and B-chain genes, alternative transcript splicing, differential mRNA stability, and translational control. Considerable progress has also been made in our understanding of PDGF receptors. Recent studies demonstrate that there are two distinct PDGF receptor genes. PDGF receptors can undergo dimerization and it has been postulated that dimerization can lead to the formation of three different receptor dimers. In addition, it appears that dimerization is required for activation of PDGF receptors and the biological activity of PDGF. Although relatively little is known about the regulation of PDGF receptors, PDGF receptors are known to be down regulated by PDGF, and expression of PDGF receptors begins relatively early during embryogenesis. Furthermore, the binding of PDGF is regulated by cell density. Unexpectedly, recent evidence suggests that PDGF can localize to the nucleus, which suggests an intranuclear function for PDGF may exist. Together, these findings imply a complex and multi-leveled regulatory scheme for controlling the production of PDGF and its receptors.

References

Westermark B, Johnsson A, Paulsson Y, Betsholtz C, Heldin C, Herlyn M . 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; 83(19):7197-200. PMC: 386682. DOI: 10.1073/pnas.83.19.7197. View

Maher D, Lee B, Donoghue D . The alternatively spliced exon of the platelet-derived growth factor A chain encodes a nuclear targeting signal. Mol Cell Biol. 1989; 9(5):2251-3. PMC: 363024. DOI: 10.1128/mcb.9.5.2251-2253.1989. View

Shaw G, Kamen R . A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986; 46(5):659-67. DOI: 10.1016/0092-8674(86)90341-7. View

Rappolee D, Brenner C, Schultz R, Mark D, Werb Z . Developmental expression of PDGF, TGF-alpha, and TGF-beta genes in preimplantation mouse embryos. Science. 1988; 241(4874):1823-5. DOI: 10.1126/science.3175624. View

Kazlauskas A, DiCorleto P . A comparison of the platelet-derived growth factor-dependent tyrosine kinase activity in sparse and confluent fibroblasts. J Cell Physiol. 1986; 126(2):225-36. DOI: 10.1002/jcp.1041260211. View

Mercola M, Melton D, Stiles C . Platelet-derived growth factor A chain is maternally encoded in Xenopus embryos. Science. 1988; 241(4870):1223-5. DOI: 10.1126/science.3413486. View

King C, Giese N, ROBBINS K, Aaronson S . In vitro mutagenesis of the v-sis transforming gene defines functional domains of its growth factor-related product. Proc Natl Acad Sci U S A. 1985; 82(16):5295-9. PMC: 390554. DOI: 10.1073/pnas.82.16.5295. View

Rakowicz-Szulczynska E, KOPROWSKI H . Identification of NGF receptor in chromatin of melanoma cells using monoclonal antibody to cell surface NGF receptor. Biochem Biophys Res Commun. 1986; 140(1):174-80. DOI: 10.1016/0006-291x(86)91073-9. View

Huang J, Huang S, Deuel T . Transforming protein of simian sarcoma virus stimulates autocrine growth of SSV-transformed cells through PDGF cell-surface receptors. Cell. 1984; 39(1):79-87. DOI: 10.1016/0092-8674(84)90193-4. View

10.

Heldin C, Ernlund A, Rorsman C, Ronnstrand L . Dimerization of B-type platelet-derived growth factor receptors occurs after ligand binding and is closely associated with receptor kinase activation. J Biol Chem. 1989; 264(15):8905-12. View

11.

Beckmann M, Betsholtz C, Heldin C, Westermark B, Di Marco E, Di Fiore P . Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains. Science. 1988; 241(4871):1346-9. DOI: 10.1126/science.2842868. View

12.

Kohler N, Lipton A . Platelets as a source of fibroblast growth-promoting activity. Exp Cell Res. 1974; 87(2):297-301. DOI: 10.1016/0014-4827(74)90484-4. View

13.

Williams L . Signal transduction by the platelet-derived growth factor receptor. Science. 1989; 243(4898):1564-70. DOI: 10.1126/science.2538922. View

14.

Seifert R, Hart C, Phillips P, Forstrom J, Ross R, Murray M . Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. J Biol Chem. 1989; 264(15):8771-8. View

15.

Rizzino A, Ruff E, Rizzino H . Induction and modulation of anchorage-independent growth by platelet-derived growth factor, fibroblast growth factor, and transforming growth factor-beta. Cancer Res. 1986; 46(6):2816-20. View

16.

Buxser S, Puma P, Johnson G . Properties of the nerve growth factor receptor. Relationship between receptor structure and affinity. J Biol Chem. 1985; 260(3):1917-26. View

17.

Ross R, GLOMSET J, Kariya B, Harker L . A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc Natl Acad Sci U S A. 1974; 71(4):1207-10. PMC: 388193. DOI: 10.1073/pnas.71.4.1207. View

18.

Paulsson Y, Austgulen R, Hofsli E, Heldin C, Westermark B, Nissen-Meyer J . Tumor necrosis factor-induced expression of platelet-derived growth factor A-chain messenger RNA in fibroblasts. Exp Cell Res. 1989; 180(2):490-6. DOI: 10.1016/0014-4827(89)90075-x. View

19.

Gronwald R, Seifert R, Bowen-Pope D . Differential regulation of expression of two platelet-derived growth factor receptor subunits by transforming growth factor-beta. J Biol Chem. 1989; 264(14):8120-5. View

20.

Starksen N, Harsh 4th G, Gibbs V, Williams L . Regulated expression of the platelet-derived growth factor A chain gene in microvascular endothelial cells. J Biol Chem. 1987; 262(30):14381-4. View