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Pdgfrb  -  platelet derived growth factor receptor,...

Mus musculus

Synonyms: AI528809, Beta platelet-derived growth factor receptor, Beta-type platelet-derived growth factor receptor, CD140 antigen-like family member B, CD140b, ...
 
 
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Disease relevance of Pdgfrb

 

High impact information on Pdgfrb

  • Complete loss of function of both ligands, therefore, phenocopied the loss of PDGFR-alpha function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-alpha to regulate the development of craniofacial structures, the neural tube and mesodermal organs [6].
  • However, targetted inactivation of the Pdgfb gene or the Pdgf receptor beta (Pdgfrb) gene, by homologous recombination, does not prevent the development of apparently normal large arteries and connective tissue [7].
  • Pdgfrb inactivation did not affect cell contribution to non-muscle mesodermal lineages, including fibroblasts and endothelial cells [7].
  • This study revealed that the participation of Pdgfrb(-/-) cells in all muscle lineages (smooth, cardiac, skeletal and pericyte) was reduced by eightfold compared with Pdgfrb(+/+) cells, and that participation of Pdgfrb(+/-) cells was reduced by twofold (eightfold for pericytes) [7].
  • The Akt activation was also shown to depend on PDGFR beta tyrosines Y740 and Y751, which bind phosphatidylinositol 3-kinase (PI 3-kinase) upon phosphorylation [8].
 

Chemical compound and disease context of Pdgfrb

  • Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were also suppressed by repeated intrathecal injection of either the PDGF alpha receptor (PDGFRalpha)/Fc chimera protein or the PDGFR-dependent tyrosine kinase inhibitor AG17 [(3,5-di-tert-butyl-4-hydroxybenzylidene)-malononitrile] [9].
  • Inactivation of LRP1 in vascular SMCs of mice causes PDGFR overexpression and abnormal activation of PDGFR signaling, resulting in disruption of the elastic layer, SMC proliferation, aneurysm formation, and marked susceptibility to cholesterol-induced atherosclerosis [10].
 

Biological context of Pdgfrb

  • The c-Abl nonreceptor tyrosine kinase is activated by growth factor signals such as the platelet-derived growth factor (PDGF) and functions downstream of the PDGF-beta receptor (PDGFR) to mediate biological processes such as membrane ruffling, mitogenesis, and chemotaxis [11].
  • The findings suggest that Shb may play a crucial role during early ES cell differentiation to vascular structures by transducing VEGFR-2 and PDGFR-beta signals [12].
  • However, the importance of individual PDGFR-beta signal transduction pathways in vivo is not known [13].
  • A mutant PDGFR chimera that was not able to detectably associate with or activate Src was compromised in its ability to mediate tyrosine phosphorylation of receptor-associated signaling molecules and initiated a submaximal activation of Erk [14].
  • This study demonstrates that hematopoietic PDGF-B or PDGFR beta expression is not required for hematopoiesis or integrity of the cardiovascular system [15].
 

Anatomical context of Pdgfrb

 

Associations of Pdgfrb with chemical compounds

 

Physical interactions of Pdgfrb

 

Regulatory relationships of Pdgfrb

  • PDGF-A chain homodimer PDGF AA activates alpha-PDGFR only, and its role for cell migration is still debatable [24].
  • 1O2 treatment did not induce phosphorylation of platelet-derived growth factor receptor (PDGFR) or activate SH-PTP2, a substrate of growth factor receptors, suggesting that PDGFR was not activated [25].
  • Together these results indicate that RGS5 exerts control over PDGFR-beta and GPCR-mediated signaling pathways active during fetal vascular maturation [26].
  • We conclude that TGF-beta regulates PDGFR alpha in the mammary stroma via a c-Cbl-independent mechanism [27].
  • In fact, either cytokine deprivation of IL-3-dependent Ba/F3 cells or exposure of TEL/PDGFRbeta-expressing cells to the specific inhibitor of the PDGFR tyrosine kinase, CGP53716, caused a strong decrease in NF-kappaB activity followed by extensive cell death [28].
 

Other interactions of Pdgfrb

  • Moreover, c-Abl and Arg, in turn, phosphorylate the PDGFR [11].
  • The results position Fbn2 between the D18Mit35 and Pdgfrb loci in the central region of mouse Chr 18 [29].
  • A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling [6].
  • In Ang-2 null mutants, alpha SMA, desmin, and PDGFR beta prominently immunolocalized in cortical peritubular locations [30].
  • Some alpha SMA-positive cells were closely associated with CD31- and Tie-2-positive peritubular capillary endothelia, and some of the alpha SMA-positive cells expressed PDGFR beta, desmin, and neural/glial cell 2 (NG2), consistent with a pericyte-like identity [30].
 

Analytical, diagnostic and therapeutic context of Pdgfrb

References

  1. Dose-dependent effects of platelet-derived growth factor-B on glial tumorigenesis. Shih, A.H., Dai, C., Hu, X., Rosenblum, M.K., Koutcher, J.A., Holland, E.C. Cancer Res. (2004) [Pubmed]
  2. Inhibition of PDGFR phosphorylation and Src and Akt activity by GN963 leads to therapy of human pancreatic cancer growing orthotopically in nude mice. Baker, C.H., Trevino, J.G., Summy, J.M., Zhang, F., Caron, A., Nesbit, M., Gallick, G.E., Fidler, I.J. Int. J. Oncol. (2006) [Pubmed]
  3. Functional blockade of platelet-derived growth factor receptor-beta but not of receptor-alpha prevents vascular smooth muscle cell accumulation in fibrous cap lesions in apolipoprotein E-deficient mice. Sano, H., Sudo, T., Yokode, M., Murayama, T., Kataoka, H., Takakura, N., Nishikawa, S., Nishikawa, S.I., Kita, T. Circulation (2001) [Pubmed]
  4. Targeting platelet-derived growth factor receptor on endothelial cells of multidrug-resistant prostate cancer. Kim, S.J., Uehara, H., Yazici, S., Busby, J.E., Nakamura, T., He, J., Maya, M., Logothetis, C., Mathew, P., Wang, X., Do, K.A., Fan, D., Fidler, I.J. J. Natl. Cancer Inst. (2006) [Pubmed]
  5. Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Roberts, W.G., Whalen, P.M., Soderstrom, E., Moraski, G., Lyssikatos, J.P., Wang, H.F., Cooper, B., Baker, D.A., Savage, D., Dalvie, D., Atherton, J.A., Ralston, S., Szewc, R., Kath, J.C., Lin, J., Soderstrom, C., Tkalcevic, G., Cohen, B.D., Pollack, V., Barth, W., Hungerford, W., Ung, E. Cancer Res. (2005) [Pubmed]
  6. 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]
  7. Chimaeric analysis reveals role of Pdgf receptors in all muscle lineages. Crosby, J.R., Seifert, R.A., Soriano, P., Bowen-Pope, D.F. Nat. Genet. (1998) [Pubmed]
  8. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Franke, T.F., Yang, S.I., Chan, T.O., Datta, K., Kazlauskas, A., Morrison, D.K., Kaplan, D.R., Tsichlis, P.N. Cell (1995) [Pubmed]
  9. Protease-activated receptor-1 and platelet-derived growth factor in spinal cord neurons are implicated in neuropathic pain after nerve injury. Narita, M., Usui, A., Narita, M., Niikura, K., Nozaki, H., Khotib, J., Nagumo, Y., Yajima, Y., Suzuki, T. J. Neurosci. (2005) [Pubmed]
  10. LRP: role in vascular wall integrity and protection from atherosclerosis. Boucher, P., Gotthardt, M., Li, W.P., Anderson, R.G., Herz, J. Science (2003) [Pubmed]
  11. Bidirectional signaling links the Abelson kinases to the platelet-derived growth factor receptor. Plattner, R., Koleske, A.J., Kazlauskas, A., Pendergast, A.M. Mol. Cell. Biol. (2004) [Pubmed]
  12. Shb promotes blood vessel formation in embryoid bodies by augmenting vascular endothelial growth factor receptor-2 and platelet-derived growth factor receptor-beta signaling. Rolny, C., Lu, L., Agren, N., Nilsson, I., Roe, C., Webb, G.C., Welsh, M. Exp. Cell Res. (2005) [Pubmed]
  13. Retention of PDGFR-beta function in mice in the absence of phosphatidylinositol 3'-kinase and phospholipase Cgamma signaling pathways. Tallquist, M.D., Klinghoffer, R.A., Heuchel, R., Mueting-Nelsen, P.F., Corrin, P.D., Heldin, C.H., Johnson, R.J., Soriano, P. Genes Dev. (2000) [Pubmed]
  14. Activation of Src family members is not required for the platelet-derived growth factor beta receptor to initiate mitogenesis. DeMali, K.A., Kazlauskas, A. Mol. Cell. Biol. (1998) [Pubmed]
  15. Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF beta-receptor null mice. Kaminski, W.E., Lindahl, P., Lin, N.L., Broudy, V.C., Crosby, J.R., Hellström, M., Swolin, B., Bowen-Pope, D.F., Martin, P.J., Ross, R., Betsholtz, C., Raines, E.W. Blood (2001) [Pubmed]
  16. Molecular profiles of the mouse postnatal development of the esophageal epithelium showing delayed growth start. Daiko, H., Isohata, N., Sano, M., Aoyagi, K., Ogawa, K., Kameoka, S., Yoshida, T., Sasaki, H. Int. J. Mol. Med. (2006) [Pubmed]
  17. A colony-stimulating factor 1 (CSF-1) receptor/platelet-derived growth factor-beta receptor gene fusion confers CSF-1 independence and tumorigenicity on a c-myc-immortalized monocyte cell line. Eccles, M.R., King, F.J., Cole, M.D. Mol. Cell. Biol. (1992) [Pubmed]
  18. Differences in substrate specificities of alpha and beta platelet-derived growth factor (PDGF) receptors. Correlation with their ability to mediate PDGF transforming functions. Heidaran, M.A., Beeler, J.F., Yu, J.C., Ishibashi, T., LaRochelle, W.J., Pierce, J.H., Aaronson, S.A. J. Biol. Chem. (1993) [Pubmed]
  19. p73 competes with co-activators and recruits histone deacetylase to NF-Y in the repression of PDGF beta-receptor. Uramoto, H., Wetterskog, D., Hackzell, A., Matsumoto, Y., Funa, K. J. Cell. Sci. (2004) [Pubmed]
  20. The S1P2 receptor negatively regulates platelet-derived growth factor-induced motility and proliferation. Goparaju, S.K., Jolly, P.S., Watterson, K.R., Bektas, M., Alvarez, S., Sarkar, S., Mel, L., Ishii, I., Chun, J., Milstien, S., Spiegel, S. Mol. Cell. Biol. (2005) [Pubmed]
  21. Aberrant expression of PDGF ligands and receptors in the tumor prone ovary of follitropin receptor knockout (FORKO) mouse. Chen, X., Aravindakshan, J., Yang, Y., Tiwari-Pandey, R., Sairam, M.R. Carcinogenesis (2006) [Pubmed]
  22. Src family kinases are required for integrin but not PDGFR signal transduction. Klinghoffer, R.A., Sachsenmaier, C., Cooper, J.A., Soriano, P. EMBO J. (1999) [Pubmed]
  23. Functional importance of platelet-derived growth factor (PDGF) receptor extracellular immunoglobulin-like domains. Identification of PDGF binding site and neutralizing monoclonal antibodies. Lokker, N.A., O'Hare, J.P., Barsoumian, A., Tomlinson, J.E., Ramakrishnan, V., Fretto, L.J., Giese, N.A. J. Biol. Chem. (1997) [Pubmed]
  24. Both platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta promote murine fibroblast cell migration. Yu, J., Moon, A., Kim, H.R. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  25. Singlet oxygen-induced activation of Akt/protein kinase B is independent of growth factor receptors. Zhuang, S., Kochevar, I.E. Photochem. Photobiol. (2003) [Pubmed]
  26. Pericyte-specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation. Cho, H., Kozasa, T., Bondjers, C., Betsholtz, C., Kehrl, J.H. FASEB J. (2003) [Pubmed]
  27. TGF-beta, c-Cbl, and PDGFR-alpha the in mammary stroma. Crowley, M.R., Bowtell, D., Serra, R. Dev. Biol. (2005) [Pubmed]
  28. Evidence for a role of NF-kappaB in the survival of hematopoietic cells mediated by interleukin 3 and the oncogenic TEL/platelet-derived growth factor receptor beta fusion protein. Besançon, F., Atfi, A., Gespach, C., Cayre, Y.E., Bourgeade, M.F. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  29. Of mice and Marfan: genetic linkage analyses of the fibrillin genes, Fbn1 and Fbn2, in the mouse genome. Goldstein, C., Liaw, P., Jimenez, S.A., Buchberg, A.M., Siracusa, L.D. Mamm. Genome (1994) [Pubmed]
  30. Dysmorphogenesis of kidney cortical peritubular capillaries in angiopoietin-2-deficient mice. Pitera, J.E., Woolf, A.S., Gale, N.W., Yancopoulos, G.D., Yuan, H.T. Am. J. Pathol. (2004) [Pubmed]
  31. Expression of platelet-derived growth factor (PDGF) in the epididymis and analysis of the epididymal development in PDGF-A, PDGF-B, and PDGF receptor beta deficient mice. Basciani, S., Mariani, S., Arizzi, M., Brama, M., Ricci, A., Betsholtz, C., Bondjers, C., Ricci, G., Catizone, A., Galdieri, M., Spera, G., Gnessi, L. Biol. Reprod. (2004) [Pubmed]
  32. SU14813: a novel multiple receptor tyrosine kinase inhibitor with potent antiangiogenic and antitumor activity. Patyna, S., Laird, A.D., Mendel, D.B., O'farrell, A.M., Liang, C., Guan, H., Vojkovsky, T., Vasile, S., Wang, X., Chen, J., Grazzini, M., Yang, C.Y., Haznedar, J.O., Sukbuntherng, J., Zhong, W.Z., Cherrington, J.M., Hu-Lowe, D. Mol. Cancer Ther. (2006) [Pubmed]
  33. Leptin affects oligodendroglial development in the mouse embryonic cerebral cortex. Udagawa, J., Nimura, M., Otani, H. Neuro Endocrinol. Lett. (2006) [Pubmed]
  34. Down-regulation of platelet-derived growth factor receptor expression during terminal differentiation of 3T3-L1 pre-adipocyte fibroblasts. Vaziri, C., Faller, D.V. J. Biol. Chem. (1996) [Pubmed]
  35. Downregulation of platelet-derived growth factor receptor-beta in Shp-2 mutant fibroblast cell lines. Lu, X., Qu, C.K., Shi, Z.Q., Feng, G.S. Oncogene (1998) [Pubmed]
 
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