Platelet Derived Growth Factor

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Platelet-derived growth factor BB, Human.

The name Platelet-derived growth factor ( PDGF , "growth factor from platelets ") stands for a family of four growth factors ( PDGF-A , PDGF-B , PDGF-C and PDGF-D ), all of which act as a mitogen on cells that originate in the embryonic connective tissue . They are released when platelets are injured to stimulate tissue healing and play an important role in embryogenesis .

function

PDGF plays a role in embryogenesis (particularly in kidney, blood vessel, lungs, and CNS development ), cell proliferation , cell migration , wound healing, and angiogenesis, and is also associated with various diseases such as atherosclerosis , fibrosis, and cancer. A retroviral homolog of PDGF-B (v-sis) is found in the genome of a monkey virus that causes sarcomas (WMSV, Woolly Monkey Sarcoma Virus) and is jointly responsible for tumor development.

The growth factors usually appear as dimers (homo- or heterodimers), which are connected by two disulfide bridges , and thus each bind to two receptors. This brings the receptors close enough together that they can phosphorylate each other on tyrosines . In this way, they then activate phosphorylate other proteins inside the cell on specific tyrosines and pass the signal on, whereby they also activate the PI 3-kinase signaling pathway (see also receptor tyrosine kinase ).

PDGF receptors (PDGFRs) are found in various cells, among other things, fibroblasts are stimulated to cell division by PDGF (although PDGF alone is not sufficient to complete cell division successfully).

history

In 1974, Ross and co-workers discovered that a factor produced by platelets was very effective in stimulating monkey smooth muscle cell growth. This factor was called platelet-derived growth factor because of its occurrence and since then has contributed a lot to the understanding of signal transduction . While the classic PDGFs A and B have been known for a long time, PDGF-C (2000) and PDGF-D (2001) were only discovered at the beginning of the 21st century.

evolution

The PDGF family is so closely related to the VEGF family that the two are often grouped together as the PDGF / VEGF family. In invertebrates , the molecules of these two families cannot be easily distinguished from one another and they are therefore collectively referred to as PVFs (PDGF / VEGF-like growth factors).

See also

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  1. ^ A b X. Li, U. Eriksson: Novel PDGF family members: PDGF-C and PDGF-D . In: Cytokine Growth Factor Rev. Volume 14 , no. 2 , April 2003, p. 91-98 , PMID 12651221 .
  2. ^ CH Heldin, B. Westermark: Mechanism of action and in vivo role of platelet-derived growth facto. In: Physiol Rev . 79 (4), 1999 Oct, pp. 1283-1316. PMID 10508235
  3. ^ LT Williams: The sis gene and PDGF . In: Cancer Surveys . 5, No. 2, 1986, ISSN  0261-2429 , pp. 233-241. PMID 3536086 .
  4. ↑ M. Andersson, A. Ostman, G. Bäckström, U. Hellman, C. George-Nascimento, B. Westermark, CH Heldin: Assignment of interchain disulfide bonds in platelet-derived growth factor (PDGF) and evidence for agonist activity of monomeric PDGF. In: J. Biol. Chem. 267 (16), 1992, pp 11260-11266. PMID 1317862
  5. ↑ It is certainly interesting that PDGF has a strong stimulating effect on cell proliferation , but in the absence of other factors the cell goes into apoptotic cell death instead of proliferating. See: Kim et al.: Platelet-derived growth factor induces apoptosis in growth-arrested murine fibroblasts. In: Proc Natl Acad Sci USA . 92 (21), 1995 October 10, pp. 9500-9504. PMID 7568162
  6. ↑ R. Ross, J. Glomset, as Kariya, L. Harker: A platelet-dependent, serum Factor That Stimulates the Proliferation of Arterial Smooth Muscle Cells In Vitro. In: Proc Natl Acad Sci U.S.A. 71 (4), 1974 Apr, pp. 1207-1210. PMID 4208546
  7. ↑ X. Li, A. Ponten, K. Aase, L. Karlsson, A. Abramsson, M. Uutela, G. Backstrom, M. Hellstrom, H. Bostrom, H. Li, P. Soriano, C. Betsholtz , CH Heldin, K. Alitalo , A. Ostman, U. Eriksson: PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. In: Nat Cell Biol . 2 (5), 2000 May, pp. 302-309. PMID 10806482
  8. ↑ E. Bergsten M. Uutela, X. Li, K. Pietras, A. Ostman, CH heroine, K. Alitalo , U. Eriksson: PDGF-D is a specific, protease-activated ligand for the PDGF-beta receptor. In: Nat Cell Biol. 3 (5), 2001 May, pp. 512-516. PMID 11331881 .
  9. ↑ Tarsitano M, De Falco S, Colonna V, McGhee JD, Persico MG: The C. elegans pvf-1 gene encodes a PDGF / VEGF-like factor able to bind mammalian VEGF receptors and to induce angiogenesis . In: FASEB Journal . tape 20 , no. 2 , 2006, p. 227-233 , doi : 10.1096 / fj.05-4147com .