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Gene Review

Pdgfra  -  platelet derived growth factor receptor,...

Mus musculus

Synonyms: AI115593, Alpha platelet-derived growth factor receptor, Alpha-type platelet-derived growth factor receptor, CD140 antigen-like family member A, CD140a, ...
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High impact information on Pdgfra

  • This phenotype was less severe than that of Pdgfra(-/-) embryos [1].
  • Our data indicate that specific combinations of naturally occurring PDGFRA promoter haplotypes strongly affect NTD genesis [2].
  • Whereas the order of the RTK genes was determined as Pdgfra-c-kit-flk1, analysis of the Wsh mutation revealed that the c-kit and Pdgfra genes are unlinked in Wsh, presumably because of an inversion of a small segment of chromosome 5 [3].
  • The map indicates the position of the Ph deletion, which encompasses not more than 400 kb around and including the Pdgfra gene [4].
  • The map also places the distal breakpoint of the Rw inversion to a limited chromosomal segment between Kit and Pdgfra [4].

Biological context of Pdgfra

  • By using mouse-Chinese hamster somatic cell hybrids and haplotype analysis in interspecific backcross mice, mouse Pdgfra was mapped to chromosome 5 in tight linkage with Kit [5].
  • Out of 16 fetuses analyzed, Pdgfra genomic sequences were absent and no mRNA for the receptor was detected in 6 fetuses that were developmentally abnormal (the presumptive Ph homozygotes) [6].
  • The alpha receptor of PDGF (Pdgfra) is expressed in primitive endoderm and mesoderm derivatives throughout embryogenesis [7].
  • The expression patterns were basically similar in the 2.2 and 0.9 kb lines and overlapped grossly the endogenous Pdgfra gene expression pattern [8].
  • Our results demonstrate that Gli1 is not required to induce Pdgfra expression during embryonic bone development, and are consistent with previous findings that Pdgfralpha and Hh pathways serve different functions in, e.g., bone, gut, and lung development [9].

Anatomical context of Pdgfra

  • Pdgfra-positive progenitors later spread through the forebrain into areas where Shh is not expressed, including the cerebral cortex [10].
  • We report that PDGF-A and Pdgfra are expressed in separate, but adjacent cell layers in these structures and that in most, the ligand is expressed in the epithelium, whereas the receptor in the mesenchyme [11].
  • Gli1 and Pdgfra were also expressed differently in the developing lung, heart, central nervous system, skin, tooth, and eye [9].
  • Consistent with this finding, LPA raised the ratio of beta-tubulin type III-positive young neurons and reduced the ratio of CD140a-positive oligodendrocyte precursors in neurospheres [12].
  • Therefore, we can postulate that Dex-induced fibroblast proliferation is mediated, at least in part, by PDGF-AA, which binds to the PDGF-R alpha [13].

Associations of Pdgfra with chemical compounds

  • Thus the W19H deletion removes at least two receptor tyrosine kinases and the results suggest Pdgfra as a candidate for the Ph locus [5].
  • Although the inhibitory effect of imatinib on various types of activating mutant KIT has been well examined, that on the activating mutant PDGFRA has not been fully investigated [14].
  • Previously, we found 2 types of gain-of-function mutation of the PDGFRA gene, Val561 to Asp and Asp842 to Val, in about half of GISTs without c-kit gene mutations [14].

Enzymatic interactions of Pdgfra

  • Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation [6].

Regulatory relationships of Pdgfra

  • Furthermore, we present evidence that both Kit and Pdgfra are expressed from the Rw chromosome in several adult tissues [15].
  • To investigate if the Shh signaling pathway is involved in the tightly regulated Pdgfra expression during embryogenesis, we systematically compared Gli1 and Pdgfralpha mRNA expression patterns in vivo from mouse embryonic day 9.5 to 14 [9].

Other interactions of Pdgfra

  • Chromosomal mapping shows that the Flk-1, Kit, and Pdgfra genes are closely linked [16].
  • However, we cannot exclude the possibility that Glis can have more complex regulatory effects on Pdgfra gene activity, nor can we exclude such effects in pathological conditions [9].
  • Examples are genes from the PAX family, T (Brachyury), BRCA1 and PDGFRA genes [17].
  • One of the genes was the alpha subunit of the platelet-derived growth factor receptor (Pdgfra); another showed homology to DnaJ and cAMP response element-binding protein 2 (CREB2); and a third was novel [18].

Analytical, diagnostic and therapeutic context of Pdgfra


  1. A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling. Ding, H., Wu, X., Boström, H., Kim, I., Wong, N., Tsoi, B., O'Rourke, M., Koh, G.Y., Soriano, P., Betsholtz, C., Hart, T.C., Marazita, M.L., Field, L.L., Tam, P.P., Nagy, A. Nat. Genet. (2004) [Pubmed]
  2. Promoter haplotype combinations of the platelet-derived growth factor alpha-receptor gene predispose to human neural tube defects. Joosten, P.H., Toepoel, M., Mariman, E.C., Van Zoelen, E.J. Nat. Genet. (2001) [Pubmed]
  3. The Wsh and Ph mutations affect the c-kit expression profile: c-kit misexpression in embryogenesis impairs melanogenesis in Wsh and Ph mutant mice. Duttlinger, R., Manova, K., Berrozpe, G., Chu, T.Y., DeLeon, V., Timokhina, I., Chaganti, R.S., Zelenetz, A.D., Bachvarova, R.F., Besmer, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  4. Structural analysis of chromosomal rearrangements associated with the developmental mutations Ph, W19H, and Rw on mouse chromosome 5. Nagle, D.L., Martin-DeLeon, P., Hough, R.B., Bućan, M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  5. Mouse platelet-derived growth factor receptor alpha gene is deleted in W19H and patch mutations on chromosome 5. Smith, E.A., Seldin, M.F., Martinez, L., Watson, M.L., Choudhury, G.G., Lalley, P.A., Pierce, J., Aaronson, S., Barker, J., Naylor, S.L. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  6. Platelet-derived growth factor receptor alpha-subunit gene (Pdgfra) is deleted in the mouse patch (Ph) mutation. Stephenson, D.A., Mercola, M., Anderson, E., Wang, C.Y., Stiles, C.D., Bowen-Pope, D.F., Chapman, V.M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  7. Developmental expression of the alpha receptor for platelet-derived growth factor, which is deleted in the embryonic lethal Patch mutation. Orr-Urtreger, A., Bedford, M.T., Do, M.S., Eisenbach, L., Lonai, P. Development (1992) [Pubmed]
  8. Specific expression in mouse mesoderm- and neural crest-derived tissues of a human PDGFRA promoter/lacZ transgene. Zhang, X.Q., Afink, G.B., Svensson, K., Jacobs, J.J., Günther, T., Forsberg-Nilsson, K., van Zoelen, E.J., Westermark, B., Nistér, M. Mech. Dev. (1998) [Pubmed]
  9. Gli1 is not required for Pdgfralpha expression during mouse embryonic development. Zhang, X.Q., Afink, G.B., Hu, X.R., Forsberg-Nilsson, K., Nistér, M. Differentiation (2005) [Pubmed]
  10. Hedgehog-dependent oligodendrocyte lineage specification in the telencephalon. Tekki-Kessaris, N., Woodruff, R., Hall, A.C., Gaffield, W., Kimura, S., Stiles, C.D., Rowitch, D.H., Richardson, W.D. Development (2001) [Pubmed]
  11. Platelet-derived growth factor-A and its receptor are expressed in separate, but adjacent cell layers of the mouse embryo. Orr-Urtreger, A., Lonai, P. Development (1992) [Pubmed]
  12. Lysophosphatidic acid stimulates neuronal differentiation of cortical neuroblasts through the LPA(1)-G(i/o) pathway. Fukushima, N., Shano, S., Moriyama, R., Chun, J. Neurochem. Int. (2007) [Pubmed]
  13. Dexamethasone activates expression of the PDGF-alpha receptor and induces lung fibroblast proliferation. Warshamana, G.S., Martinez, S., Lasky, J.A., Corti, M., Brody, A.R. Am. J. Physiol. (1998) [Pubmed]
  14. Different inhibitory effect of imatinib on phosphorylation of mitogen-activated protein kinase and Akt and on proliferation in cells expressing different types of mutant platelet-derived growth factor receptor-alpha. Ohashi, A., Kinoshita, K., Isozaki, K., Nishida, T., Shinomura, Y., Kitamura, Y., Hirota, S. Int. J. Cancer (2004) [Pubmed]
  15. Lethality of Rw/Rw mouse embryos during early postimplantation development. Bućan, M., Nagle, D.L., Hough, R.B., Chapman, V.M., Lo, C.W. Dev. Biol. (1995) [Pubmed]
  16. A receptor tyrosine kinase cDNA isolated from a population of enriched primitive hematopoietic cells and exhibiting close genetic linkage to c-kit. Matthews, W., Jordan, C.T., Gavin, M., Jenkins, N.A., Copeland, N.G., Lemischka, I.R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  17. Genetic basis of neural tube defects. I. Regulatory genes for the neurulation process. Gos, M., Szpecht-Potocka, A. J. Appl. Genet. (2002) [Pubmed]
  18. Genes regulated by learning in the hippocampus. Leil, T.A., Ossadtchi, A., Nichols, T.E., Leahy, R.M., Smith, D.J. J. Neurosci. Res. (2003) [Pubmed]
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