Platelet-derived growth factor

Platelet-derived growth factor
Platelet-derived growth factor (PDGF)
Symbol PDGF
Pfam PF00341
InterPro IPR000072
SCOP 1pdg

In molecular biology, platelet-derived growth factor (PDGF) is one of the numerous growth factors, or proteins that regulate cell growth and division. In particular, it plays a significant role in blood vessel formation (angiogenesis), the growth of blood vessels from already-existing blood vessel tissue. Uncontrolled angiogenesis is a characteristic of cancer. In chemical terms, platelet-derived growth factor is dimeric glycoprotein composed of two A (-AA) or two B (-BB) chains or a combination of the two (-AB).

PDGF[1][2] is a potent mitogen for cells of mesenchymal origin, including smooth muscle cells and glial cells. In both mouse and human, the PDGF signalling network consists of four ligands, PDGFA-D, and two receptors, PDGFRalpha and PDGFRbeta. All PDGFs function as secreted, disulphide-linked homodimers, but only PDGFA and B can form functional heterodimers.

Though it is synthesized[3] stored and released by platelets upon activation, it is produced by a plethora of cells including smooth muscle cells, activated macrophages, and endothelial cells[4]



There are five different isoforms of PDGF that activate cellular response through two different receptors. Known ligands include A (PDGFA), B (PDGFB), C (PDGFC), and D (PDGFD), and an AB heterodimer and receptors alpha (PDGFRA) and beta (PDGFRB). PDGF has few other members of the family, for example VEGF sub-family.


The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), a type of cell surface receptor. Two types of PDGFRs have been identified: alpha-type and beta-type PDGFRs.[5] The alpha type binds to PDGF-AA, PDGF-BB and PDGF-AB, whereas the beta type PDGFR binds with high affinity to PDGF-BB and PDGF-AB.[6] PDGF binds to PDGFRs ligand binding pocket located within the second and third immunoglobulin domains.[7] Upon activation by PDGF, these receptors dimerise, and are "switched on" by auto-phosphorylation of several sites on their cytosolic domains, which serve to mediate binding of cofactors and subsequently activate signal transduction, for example, through the PI3K pathway. Downstream effects of this include regulation of gene expression and the cell cycle. The role of PI3K has been investigated by several laboratories. Accumulating data suggests that, while this molecule is, in general, part of growth signaling complex, it plays a more profound role in controlling cell migration.[8] The different ligand isoforms have variable affinities for the receptor isoforms, and the receptor isoforms may variably form hetero- or homo- dimers. This leads to specificity of downstream signaling. It has been shown that the cis oncogene is derived from the PDGF B-chain gene. PDGF-BB is the highest-affinity ligand for the PDGFR-beta; PDGFR-beta is a key marker of hepatic stellate cell activation in the process of fibrogenesis.[citation needed]


PDGFs are mitogenic during early developmental stages, driving the proliferation of undifferentiated mesenchyme and some progenitor populations. During later maturation stages, PDGF signalling has been implicated in tissue remodelling and cellular differentiation, and in inductive events involved in patterning and morphogenesis. In addition to driving mesenchymal proliferation, PDGFs have been shown to direct the migration, differentiation and function of a variety of specialised mesenchymal and migratory cell types, both during development and in the adult animal.[9] Other growth factors in this family include vascular endothelial growth factors B and C (VEGF-B, VEGF-C)[10][11] which are active in angiogenesis and endothelial cell growth, and placenta growth factor (PlGF) which is also active in angiogenesis.[12]

PDGF plays a role in embryonic development, cell proliferation, cell migration, and angiogenesis.[13] PDGF has also been linked to several diseases such as atherosclerosis, fibrosis and malignant diseases.[citation needed]

In addition, PDGF is a required element in cellular division for fibroblast, a type of connective tissue cell.[citation needed] In essence, the PDGFs allow a cell to skip the G1 checkpoints in order to divide.[citation needed]

PDGF is also known to maintain proliferation of oligodendrocyte progenitor cells.[citation needed] [14][15]


PDGF was one of the first growth factors characterized,[16] and has led to an understanding of the mechanism of many growth factor signaling pathways.[citation needed]

Clinical significance

Like many other growth factors that have been linked to disease, PDGF and its receptors have provided a market for receptor antagonists to treat disease. Such antagonists include (but are not limited to) specific antibodies that target the molecule of interest, which act only in a neutralizing manner.[17]

The "c-Sis" oncogene is derived from PDGF.[15][18]

Age related downregulation of the PDGF receptor on islet beta cells has been demonstrated to prevent islet beta cell proliferation in both animal and human cells and its re-expression triggered beta cell proliferation and corrected glucose regulation via insulin secretion.[19][20]

Family members

Human genes encoding proteins that belong to the platelet-derived growth factor family include:

See also


  1. ^ Hannink M, Donoghue DJ (1989). "Structure and function of platelet-derived growth factor (PDGF) and related proteins". Biochim. Biophys. Acta 989 (1): 1–10. PMID 2546599. 
  2. ^ Heldin CH (1992). "Structural and functional studies on platelet-derived growth factor". EMBO J. 11 (12): 4251–4259. PMC 556997. PMID 1425569. 
  3. ^ Minarcik, John. "Global Path Course: Video". Retrieved 6/27/2011. 
  4. ^ Kumar, Vinay (2010). Robbins and Coltran Pathologic Basis of Disease. China: Elsevier. pp. 88–89. ISBN 978-1-4160-3121-5. 
  5. ^ Matsui T, Heidaran M, Miki T, et al. (1989). "Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes". Science 243 (4892): 800–4. doi:10.1126/science.2536956. PMID 2536956. 
  6. ^ Heidaran MA, Pierce JH, Yu JC, et al. (25 October 1991). "Role of alpha beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB". J. Biol. Chem. 266 (30): 20232–7. PMID 1657917. 
  7. ^ Heidaran MA, Pierce JH, Jensen RA, Matsui T, Aaronson SA (5 November 1990). "Chimeric alpha- and beta-platelet-derived growth factor (PDGF) receptors define three immunoglobulin-like domains of the alpha-PDGF receptor that determine PDGF-AA binding specificity". J. Biol. Chem. 265 (31): 18741–4. PMID 2172231. 
  8. ^ Yu JC, Li W, Wang LM, Uren A, Pierce JH, Heidaran MA (1995). "Differential requirement of a motif within the carboxyl-terminal domain of alpha-platelet-derived growth factor (alpha PDGF) receptor for PDGF focus forming activity chemotaxis, or growth". J. Biol. Chem. 270 (13): 7033–6. doi:10.1074/jbc.270.13.7033. PMID 7706238. 
  9. ^ Hoch RV, Soriano P (2003). "Roles of PDGF in animal development". Development 130 (20): 4769–4784. doi:10.1242/dev.00721. PMID 12952899. 
  10. ^ Joukov V, Pajusola K, Kaipainen A, Saksela O, Alitalo K, Olofsson B, von Euler G, Orpana A, Pettersson RF, Eriksson U (1996). "Vascular endothelial growth factor B, a novel growth factor for endothelial cells". Proc. Natl. Acad. Sci. U.S.A. 93 (6): 2567–2581. doi:10.1073/pnas.93.6.2576. PMC 39839. PMID 8637916. 
  11. ^ Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K (1996). "A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases". EMBO J. 15 (2): 290–298. PMC 449944. PMID 8617204. 
  12. ^ Lei KJ, Alitalo K, Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Chou JY, Persico MG, Del Vecchio S (1993). "Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14". Oncogene 8 (4): 925–931. PMID 7681160. 
  13. ^ "PDGF Pathways". Retrieved 2007-11-17. 
  14. ^ Barres BA, Hart IK, Coles HSR, Burne JF, Voyvodic JT, Richardson WD, Raff MC (1992). "Cell Death and Control of Cell Survival in the Oligodendrocyte Lineage". Cell 70 (1): 31–46. doi:10.1016/0092-8674(92)90531-G. PMID 1623522. 
  15. ^ a b MeSH Proto-Oncogene+Proteins+c-sis
  16. ^ Paul D, Lipton A, Klinger I (1971). "Serum factor requirements of normal and simian virus 40-transformed 3T3 mouse fibroplasts". Proc Natl Acad Sci U S A. 68 (3): 645–52. doi:10.1073/pnas.68.3.645. PMC 389008. PMID 5276775. 
  17. ^ Shulman T, Sauer FG, Jackman RM, Chang CN, Landolfi NF (July 1997). "An antibody reactive with domain 4 of the platelet-derived growth factor beta receptor allows BB binding while inhibiting proliferation by impairing receptor dimerization". J. Biol. Chem. 272 (28): 17400–4. doi:10.1074/jbc.272.28.17400. PMID 9211881. 
  18. ^ McClintock J, Chan I, Thaker S, Katial A, Taub F, Aotaki-Keen A, Hjelmeland L (1992). "Detection of c-sis proto-oncogene transcripts by direct enzyme-labeled cDNA probes and in situ hybridization". In Vitro Cell Dev Biol 28A (2): 102–8. doi:10.1007/BF02631013. PMID 1537750. 
  19. ^
  20. ^

External links

Wikimedia Foundation. 2010.

Нужен реферат?

Look at other dictionaries:

  • Platelet-Derived Growth Factor A — Platelet Derived Growth Factor, Untereinheit A Masse/Länge Primärstruktur 125 Aminosäuren …   Deutsch Wikipedia

  • platelet-derived growth factor — n a mitogenic growth factor that is found esp. in platelets, consists of two polypeptide chains linked by bonds containing two sulfur atoms each, stimulates cell proliferation (as in connective tissue, smooth muscle, and glia), and plays a role… …   Medical dictionary

  • platelet-derived growth factor — platelet derived growth factor. См. фактор роста тромбоцитов. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • Platelet Derived Growth Factor — Der Name Platelet derived growth factor (PDGF) steht für eine Familie von vier Wachstumsfaktoren (PDGF A, PDGF B, PDGF C und PDGF D), die alle als Mitogen auf Zellen wirken, die ihren Ursprung im embryonalen Bindegewebe haben. Sie werden bei… …   Deutsch Wikipedia

  • Platelet-derived growth factor receptor — platelet derived growth factor receptor, alpha polypeptide Identifiers Symbol PDGFRA Entrez 5156 HUGO …   Wikipedia

  • platelet-derived growth factor — (= PDGF) The major mitogen in serum for growth in culture of cells of connective tissue origin. It consists of 2 different but homologous polypeptides A and B (platelet derived growth factor30,000 D) linked by disulphide bonds. Believed to play a …   Dictionary of molecular biology

  • platelet-derived growth factor — PDGF; see growth factor …   The new mediacal dictionary

  • platelet-derived growth factor — see growth factor …   Medical dictionary

  • platelet-derived growth factor — ˈ ̷ ̷  ̷ ̷  ̷ ̷ ˌ ̷ ̷ noun : a mitogenic growth factor that is found especially in platelets, consists of two polypeptide chains linked by bonds containing two sulfur atoms each, stimulates cell proliferation (as in connective tissue, smooth… …   Useful english dictionary

  • Platelet-derived Growth Factor — Plate|let de|rived Growth Fac|tor [ pleɪtlət dɪraɪft grəʊo fæktə[r]; engl. = Plättchenwachstumsfaktor], der; s: svw. ↑ PDGF …   Universal-Lexikon

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”