Minireview: Role of Intracellular Scaffolding Proteins in the Regulation of Endocrine G Protein-coupled Receptor Signaling

Overview

Journal Mol Endocrinol

Specialties Endocrinology
Molecular Biology

Date 2015 May 6

PMID 25942107

Citations 19

Authors

Cornelia Walther

Stephen S G Ferguson

Affiliations

Soon will be listed here.

Abstract

The majority of hormones stimulates and mediates their signal transduction via G protein-coupled receptors (GPCRs). The signal is transmitted into the cell due to the association of the GPCRs with heterotrimeric G proteins, which in turn activates an extensive array of signaling pathways to regulate cell physiology. However, GPCRs also function as scaffolds for the recruitment of a variety of cytoplasmic protein-interacting proteins that bind to both the intracellular face and protein interaction motifs encoded by GPCRs. The structural scaffolding of these proteins allows GPCRs to recruit large functional complexes that serve to modulate both G protein-dependent and -independent cellular signaling pathways and modulate GPCR intracellular trafficking. This review focuses on GPCR interacting PSD95-disc large-zona occludens domain containing scaffolds in the regulation of endocrine receptor signaling as well as their potential role as therapeutic targets for the treatment of endocrinopathies.

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References

Laporte S, Oakley R, Zhang J, Holt J, Ferguson S, Caron M . The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Proc Natl Acad Sci U S A. 1999; 96(7):3712-7. PMC: 22359. DOI: 10.1073/pnas.96.7.3712. View

Prezeau L, Richman J, Edwards S, Limbird L . The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes. J Biol Chem. 1999; 274(19):13462-9. DOI: 10.1074/jbc.274.19.13462. View

Hall R, Premont R, Lefkowitz R . Heptahelical receptor signaling: beyond the G protein paradigm. J Cell Biol. 1999; 145(5):927-32. PMC: 2133121. DOI: 10.1083/jcb.145.5.927. View

COLLEDGE M, Scott J . AKAPs: from structure to function. Trends Cell Biol. 1999; 9(6):216-21. DOI: 10.1016/s0962-8924(99)01558-5. View

Smith F, Oxford G, Milgram S . Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein. J Biol Chem. 1999; 274(28):19894-900. DOI: 10.1074/jbc.274.28.19894. View

Cao T, Deacon H, Reczek D, BRETSCHER A, von Zastrow M . A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature. 1999; 401(6750):286-90. DOI: 10.1038/45816. View

Stroh T, Jackson A, Sarret P, Dal Farra C, Vincent J, Kreienkamp H . Intracellular dynamics of sst5 receptors in transfected COS-7 cells: maintenance of cell surface receptors during ligand-induced endocytosis. Endocrinology. 1999; 141(1):354-65. DOI: 10.1210/endo.141.1.7259. View

Van Der Hoeven P, Van Der Wal J, Ruurs P, van Dijk M, Van Blitterswijk J . 14-3-3 isotypes facilitate coupling of protein kinase C-zeta to Raf-1: negative regulation by 14-3-3 phosphorylation. Biochem J. 2000; 345 Pt 2:297-306. PMC: 1220759. DOI: 10.1042/0264-6021:3450297. View

DeFea K, Zalevsky J, Thoma M, Dery O, Mullins R, Bunnett N . beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol. 2000; 148(6):1267-81. PMC: 2174299. DOI: 10.1083/jcb.148.6.1267. View

10.

Ali M, Sayeski P, Bernstein K . Jak2 acts as both a STAT1 kinase and as a molecular bridge linking STAT1 to the angiotensin II AT1 receptor. J Biol Chem. 2000; 275(20):15586-93. DOI: 10.1074/jbc.M908931199. View

11.

Fraser I, Cong M, Kim J, Rollins E, Daaka Y, Lefkowitz R . Assembly of an A kinase-anchoring protein-beta(2)-adrenergic receptor complex facilitates receptor phosphorylation and signaling. Curr Biol. 2001; 10(7):409-12. DOI: 10.1016/s0960-9822(00)00419-x. View

12.

DeFea K, Vaughn Z, OBryan E, Nishijima D, Dery O, Bunnett N . The proliferative and antiapoptotic effects of substance P are facilitated by formation of a beta -arrestin-dependent scaffolding complex. Proc Natl Acad Sci U S A. 2000; 97(20):11086-91. PMC: 27152. DOI: 10.1073/pnas.190276697. View

13.

Hu L, Tang Y, Miller W, Cong M, Lau A, Lefkowitz R . beta 1-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of beta 1-adrenergic receptor interaction with N-methyl-D-aspartate receptors. J Biol Chem. 2000; 275(49):38659-66. DOI: 10.1074/jbc.M005938200. View

14.

McDonald P, Chow C, Miller W, Laporte S, Field M, Lin F . Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science. 2000; 290(5496):1574-7. DOI: 10.1126/science.290.5496.1574. View

15.

Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J . Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1. J Biol Chem. 2001; 276(16):12974-82. DOI: 10.1074/jbc.M008089200. View

16.

Sayeski P, Ali M, Frank S, Bernstein K . The angiotensin II-dependent nuclear translocation of Stat1 is mediated by the Jak2 protein motif 231YRFRR. J Biol Chem. 2001; 276(13):10556-63. DOI: 10.1074/jbc.M008856200. View

17.

Richman J, Brady A, Wang Q, Hensel J, Colbran R, Limbird L . Agonist-regulated Interaction between alpha2-adrenergic receptors and spinophilin. J Biol Chem. 2001; 276(18):15003-8. DOI: 10.1074/jbc.M011679200. View

18.

Ferguson S . Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev. 2001; 53(1):1-24. View

19.

Luttrell L, Roudabush F, Choy E, Miller W, Field M, Pierce K . Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc Natl Acad Sci U S A. 2001; 98(5):2449-54. PMC: 30158. DOI: 10.1073/pnas.041604898. View

20.

Cong M, Perry S, Lin F, Fraser I, Hu L, Chen W . Regulation of membrane targeting of the G protein-coupled receptor kinase 2 by protein kinase A and its anchoring protein AKAP79. J Biol Chem. 2001; 276(18):15192-9. DOI: 10.1074/jbc.M009130200. View