Effect of receptor kinase inactivation on the rate of internalization and degradation of PDGF and the PDGF beta-receptor - PubMed (original) (raw)

Effect of receptor kinase inactivation on the rate of internalization and degradation of PDGF and the PDGF beta-receptor

A Sorkin et al. J Cell Biol. 1991 Feb.

Abstract

The complementary DNAs for wildtype and tyrosine kinase-inactivated (K634A) forms of the PDGF beta-receptor were expressed in porcine aortic endothelial cells. We examined the internalization and degradation of ligands and receptors after exposure of receptor expressing cells to PDGF-BB, which binds to the beta-receptor with high affinity, and PDGF-AB, which binds with lower affinity. Cells expressing wildtype beta-receptors were able to internalize and degrade the receptor, as well as the ligand, after exposure to PDGF-BB or -AB. Cells expressing the kinase-inactivated mutant receptor also internalized and degraded both receptor and ligand, but with lower efficiency compared with the wildtype receptor cells. The degradation of either form of receptor was inhibited by treatment of the cells with the lysosomotropic drug chloroquine. Exposure of wildtype and K634A receptor expressing cells to PDGF-AB resulted in a twofold slower rate of internalization of this ligand as compared with PDGF-BB, whereas the relative rate of degradation was similar for the two ligands. Our data indicate that tyrosine kinase activity promotes, but is not a prerequisite for, ligand-induced internalization and degradation of the ligand-receptor complex.

PubMed Disclaimer

Similar articles

• B-type receptor for platelet-derived growth factor mediates a chemotactic response by means of ligand-induced activation of the receptor protein-tyrosine kinase.
  Westermark B, Siegbahn A, Heldin CH, Claesson-Welsh L. Westermark B, et al. Proc Natl Acad Sci U S A. 1990 Jan;87(1):128-32. doi: 10.1073/pnas.87.1.128. Proc Natl Acad Sci U S A. 1990. PMID: 2153283 Free PMC article.
• Pool of ligand-bound platelet-derived growth factor beta-receptors remain activated and tyrosine phosphorylated after internalization.
  Sorkin A, Eriksson A, Heldin CH, Westermark B, Claesson-Welsh L. Sorkin A, et al. J Cell Physiol. 1993 Aug;156(2):373-82. doi: 10.1002/jcp.1041560221. J Cell Physiol. 1993. PMID: 7688373
• Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins.
  Yokote K, Hellman U, Ekman S, Saito Y, Rönnstrand L, Saito Y, Heldin CH, Mori S. Yokote K, et al. Oncogene. 1998 Mar 12;16(10):1229-39. doi: 10.1038/sj.onc.1201641. Oncogene. 1998. PMID: 9546424
• Structural and functional aspects of platelet-derived growth factor and its receptors.
  Westermark B, Claesson-Welsh L, Heldin CH. Westermark B, et al. Ciba Found Symp. 1990;150:6-14; discussion 14-22. doi: 10.1002/9780470513927.ch2. Ciba Found Symp. 1990. PMID: 2164910 Review.
• Platelet-derived growth factor receptor: current views of the two-subunit model.
  Hart CE, Bowen-Pope DF. Hart CE, et al. J Invest Dermatol. 1990 Jun;94(6 Suppl):53S-57S. doi: 10.1111/1523-1747.ep12875065. J Invest Dermatol. 1990. PMID: 2161888 Review.

Cited by

• The lysosome as a novel therapeutic target of EGFR-mediated tumor inflammation.
  Sung WJ, Kim D, Zhu A, Cho N, Yoo HM, Noh JH, Kim KM, Lee HS, Hong J. Sung WJ, et al. Front Pharmacol. 2022 Nov 11;13:1050758. doi: 10.3389/fphar.2022.1050758. eCollection 2022. Front Pharmacol. 2022. PMID: 36438839 Free PMC article. Review.
• YAP1/TEAD1 upregulate platelet-derived growth factor receptor beta to promote vascular smooth muscle cell proliferation and neointima formation.
  Osman I, Dong K, Kang X, Yu L, Xu F, Ahmed ASI, He X, Shen J, Hu G, Zhang W, Zhou J. Osman I, et al. J Mol Cell Cardiol. 2021 Jul;156:20-32. doi: 10.1016/j.yjmcc.2021.03.005. Epub 2021 Mar 19. J Mol Cell Cardiol. 2021. PMID: 33753119 Free PMC article.
• PDGF alpha- and beta-receptors activate unique and common signal transduction pathways.
  Eriksson A, Siegbahn A, Westermark B, Heldin CH, Claesson-Welsh L. Eriksson A, et al. EMBO J. 1992 Feb;11(2):543-50. doi: 10.1002/j.1460-2075.1992.tb05085.x. EMBO J. 1992. PMID: 1311251 Free PMC article.
• Internalization of activated platelet-derived growth factor receptor-phosphatidylinositol-3' kinase complexes: potential interactions with the microtubule cytoskeleton.
  Kapeller R, Chakrabarti R, Cantley L, Fay F, Corvera S. Kapeller R, et al. Mol Cell Biol. 1993 Oct;13(10):6052-63. doi: 10.1128/mcb.13.10.6052-6063.1993. Mol Cell Biol. 1993. PMID: 8413207 Free PMC article.
• Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome pathway.
  Jeffers M, Taylor GA, Weidner KM, Omura S, Vande Woude GF. Jeffers M, et al. Mol Cell Biol. 1997 Feb;17(2):799-808. doi: 10.1128/MCB.17.2.799. Mol Cell Biol. 1997. PMID: 9001234 Free PMC article.

References

1. 1. Nature. 1962 May 5;194:495-6 - PubMed
2. 1. J Cell Biol. 1975 Dec;67(3):835-51 - PubMed
3. 1. Trends Genet. 1989 Apr;5(4):108-11 - PubMed
4. 1. J Biol Chem. 1989 May 25;264(15):8905-12 - PubMed
5. 1. J Biol Chem. 1989 May 25;264(15):8771-8 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Europe PubMed Central
  • Ovid Technologies, Inc.
  • PubMed Central
  • Silverchair Information Systems

• Molecular Biology Databases

  • GlyGen glycoinformatics resource