Transactivation of Epidermal Growth Factor Receptor by G Protein-Coupled Receptors: Recent Progress, Challenges and Future Research

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2016 Jan 16

PMID 26771606

Citations 67

Authors

Zhixiang Wang

Affiliations

Soon will be listed here.

Abstract

Both G protein-coupled receptors (GPCRs) and receptor-tyrosine kinases (RTKs) regulate large signaling networks, control multiple cell functions and are implicated in many diseases including various cancers. Both of them are also the top therapeutic targets for disease treatment. The discovery of the cross-talk between GPCRs and RTKs connects these two vast signaling networks and complicates the already complicated signaling networks that regulate cell signaling and function. In this review, we focus on the transactivation of epidermal growth factor receptor (EGFR), a subfamily of RTKs, by GPCRs. Since the first report of EGFR transactivation by GPCR, significant progress has been made including the elucidation of the mechanisms underlying the transactivation. Here, we first provide a basic picture for GPCR, EGFR and EGFR transactivation by GPCR. We then discuss the progress made in the last five years and finally provided our view of the future challenge and future researches needed to overcome these challenges.

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References

Daub H, Weiss F, Wallasch C, Ullrich A . Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature. 1996; 379(6565):557-60. DOI: 10.1038/379557a0. View

Fredriksson R, Lagerstrom M, Lundin L, Schioth H . The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol. 2003; 63(6):1256-72. DOI: 10.1124/mol.63.6.1256. View

Cattaneo F, Iaccio A, Guerra G, Montagnani S, Ammendola R . NADPH-oxidase-dependent reactive oxygen species mediate EGFR transactivation by FPRL1 in WKYMVm-stimulated human lung cancer cells. Free Radic Biol Med. 2011; 51(6):1126-36. DOI: 10.1016/j.freeradbiomed.2011.05.040. View

Tice D, Biscardi J, Nickles A, Parsons S . Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. Proc Natl Acad Sci U S A. 1999; 96(4):1415-20. PMC: 15477. DOI: 10.1073/pnas.96.4.1415. View

Burgering B, Coffer P . Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature. 1995; 376(6541):599-602. DOI: 10.1038/376599a0. View

Tanimoto T, Jin Z, Berk B . Transactivation of vascular endothelial growth factor (VEGF) receptor Flk-1/KDR is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). J Biol Chem. 2002; 277(45):42997-3001. DOI: 10.1074/jbc.M204764200. View

Reichardt H, Kaestner K, Tuckermann J, Kretz O, Wessely O, Bock R . DNA binding of the glucocorticoid receptor is not essential for survival. Cell. 1998; 93(4):531-41. DOI: 10.1016/s0092-8674(00)81183-6. View

Lemmon M, Schlessinger J . Cell signaling by receptor tyrosine kinases. Cell. 2010; 141(7):1117-34. PMC: 2914105. DOI: 10.1016/j.cell.2010.06.011. View

Girgert R, Emons G, Grundker C . Inactivation of GPR30 reduces growth of triple-negative breast cancer cells: possible application in targeted therapy. Breast Cancer Res Treat. 2012; 134(1):199-205. PMC: 3397221. DOI: 10.1007/s10549-012-1968-x. View

10.

Yu Y, Zhang M, Zhang X, Cai Q, Zhu Z, Jiang W . Transactivation of epidermal growth factor receptor through platelet-activating factor/receptor in ovarian cancer cells. J Exp Clin Cancer Res. 2014; 33:85. PMC: 4189590. DOI: 10.1186/s13046-014-0085-6. View

11.

Wang Y, Wu J, Wang Z . Akt binds to and phosphorylates phospholipase C-gamma1 in response to epidermal growth factor. Mol Biol Cell. 2006; 17(5):2267-77. PMC: 1446077. DOI: 10.1091/mbc.e05-10-0918. View

12.

Tu H, Xu C, Zhang W, Liu Q, Rondard P, Pin J . GABAB receptor activation protects neurons from apoptosis via IGF-1 receptor transactivation. J Neurosci. 2010; 30(2):749-59. PMC: 6633015. DOI: 10.1523/JNEUROSCI.2343-09.2010. View

13.

Wells A, Kassis J, Solava J, Turner T, Lauffenburger D . Growth factor-induced cell motility in tumor invasion. Acta Oncol. 2002; 41(2):124-30. DOI: 10.1080/028418602753669481. View

14.

Yu Y, Zhang X, Hong S, Zhang M, Cai Q, Jiang W . Epidermal growth factor induces platelet-activating factor production through receptors transactivation and cytosolic phospholipase A2 in ovarian cancer cells. J Ovarian Res. 2014; 7:39. PMC: 4005630. DOI: 10.1186/1757-2215-7-39. View

15.

Pawson T . New impressions of Src and Hck. Nature. 1997; 385(6617):582-3, 585. DOI: 10.1038/385582b0. View

16.

Avruch J . MAP kinase pathways: the first twenty years. Biochim Biophys Acta. 2007; 1773(8):1150-60. PMC: 2043147. DOI: 10.1016/j.bbamcr.2006.11.006. View

17.

Pawson T . Protein modules and signalling networks. Nature. 1995; 373(6515):573-80. DOI: 10.1038/373573a0. View

18.

Swift J, Godin A, Dore K, Freland L, Bouchard N, Nimmo C . Quantification of receptor tyrosine kinase transactivation through direct dimerization and surface density measurements in single cells. Proc Natl Acad Sci U S A. 2011; 108(17):7016-21. PMC: 3084083. DOI: 10.1073/pnas.1018280108. View

19.

Kurt A, Tiftik R, Un I, Ulker S, Buyukafsar K . G protein-coupled estrogen receptor1 (GPER1) may mediate Rho-kinase (ROCK-2) up-regulation in coronary endothelial cells. Endocr Regul. 2013; 47(2):75-84. DOI: 10.4149/endo_2013_02_75. View

20.

Reinehr R, Becker S, Eberle A, Grether-Beck S, Haussinger D . Involvement of NADPH oxidase isoforms and Src family kinases in CD95-dependent hepatocyte apoptosis. J Biol Chem. 2005; 280(29):27179-94. DOI: 10.1074/jbc.M414361200. View