Somatostatin activates Ras and ERK1/2 via a G protein βγ-subunit-initiated pathway in thyroid cells

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• 作者：Francisco J. Rodríguez-Álvarez ; Eva Jiménez-Mora…
• 关键词：Thyroid ; Somatostatin ; Gi proteins ; Gβγ ; Ras ; ERK1/2
• 刊名：Molecular and Cellular Biochemistry
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：411
• 期：1-2
• 页码：253-260
• 全文大小：1,089 KB
• 参考文献：1.Medina DL, Toro MJ, Santisteban P (2000) Somatostatin interferes with thyrotropin-induced G1-S transition mediated by cAMP-dependent protein kinase and phosphatidylinositol 3-kinase. Involvement of RhoA and cyclin E cyclin-dependent kinase 2 complexes. J Biol Chem 275:15549–15556CrossRef PubMed
  2.Riesco-Eizaguirre G, Santisteban P (2006) A perspective view of sodium iodide symporter research and its clinical implications. Eur J Endocrinol 155:495–512CrossRef PubMed
  3.Patel YC (1999) Somatostatin and its receptor family. Front Neuroendocrinol 20:157–198CrossRef PubMed
  4.Medina DL, Velasco JA, Santisteban P (1999) Somatostatin is expressed in FRTL-5 Thyroid cells and prevents thyrotropin-mediated down-regulation of the cyclin-dependent kinase inhibitor p27kip1. Endocrinology 140:87–95PubMed
  5.Birnbaumer L (2007) Expansion of signal transduction by G proteins. The second 15 years or so: from 3 to 16 alpha subunits plus betagamma dimers. Biochim Biophys Acta 1768:772–793PubMedCentral CrossRef PubMed
  6.Crespo P, Xu N, Simonds WF, Gutkind JS (1994) Ras-dependent activation of MAP kinase pathway mediated by G-protein βγ subunits. Nature 369:418–420CrossRef PubMed
  7.Faure M, Voyno-Yasenetskaya TA, Bourne HR (1994) cAMP and beta gamma subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. J Biol Chem 269:7851–7854PubMed
  8.Koch WJ, Hawes BE, Allen LF, Lefkowitz RJ (1994) Direct evidence that Gi-coupled receptor stimulation of mitogen-activateed protein kinase is mediated by G beta gamma activation of p21ras. Proc Natl Acad Sci USA 91:12706–12710PubMedCentral CrossRef PubMed
  9.Hwang JI, Choi S, Fraser ID, Chang MS, Simon MI (2005) Silencing the expression of multiple Gbeta-subunits eliminates signaling mediated by all four families of G proteins. Proc Natl Acad Sci USA 102:9493–9498PubMedCentral CrossRef PubMed
  10.Van Biesen T, Hawes BE, Luttrell DK, Krueger KM, Touhara K, Porfiri E et al (1995) Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway. Nature 376:781–784CrossRef PubMed
  11.Craddock BL, Hobbs J, Edmead CE, Welham MJ (2001) Phosphoinositide 3-kinase-dependent regulation of interleukin-3-induced proliferation: involvement of mitogen-activated protein kinases, SHP2 and Gab2. J Biol Chem 276:24274–24283CrossRef PubMed
  12.Ferjoux G, Lopez F, Esteve JP, Ferrand A, Vivier E, Vely F et al (2003) Critical role of Src and SHP-2 in sst2 somatostatin receptor-mediated activation of SHP-1 and inhibition of cell proliferation. Mol Biol Cell 14:3911–3928PubMedCentral CrossRef PubMed
  13.Schmitt JM, Stork PJ (2002) Galpha and Gbeta gamma require distinct Src-dependent pathways to activate Rap1 and Ras. J Biol Chem 277:43024–43032CrossRef PubMed
  14.Jin M, Min C, Zheng M, Cho DI, Cheong SJ, Kurose H, Kim KM et al (2013) Multiple signaling routes involved in the regulation of adenylyl cyclase and extracellular regulated kinase by dopamine D(2) and D(3) receptors. Pharmacol Res 67:31–41CrossRef PubMed
  15.Vidal M, Wieland T, Lohse MJ, Lorenz K (2012) β-Adrenergic receptor stimulation causes cardiac hypertrophy via a Gβγ/Erk-dependent pathway. Cardiovasc Res 96:255–264CrossRef PubMed
  16.Ciullo I, Diez-Roux G, Di Domenico M, Migliaccio A, Avvedimento EV (2001) cAMP signaling selectively influences Ras effectors pathways. Oncogene 20:1186–1192CrossRef PubMed
  17.Iacovelli L, Capobianco L, Salvatore L, Sallese M, D′Ancona GM, de Blasi A (2001) Thyrotropin activates Mitogen-activated protein kinase pathway in FRTL-5 by a cAMP-dependent protein kinase A-independent mechanism. Mol Pharmacol 60:924–933PubMed
  18.Cattaneo MG, Taylor JE, Culler MD, Nisoli E, Vicentini LM (2000) Selective stimulation of somatostatin receptor subtypes: differential effects on Ras/MAP kinase pathway and cell proliferation in human neuroblastoma cells. FEBS Lett 481:271–276CrossRef PubMed
  19.Florio T, Yao Y, Carey KD, Dillon TJ, Stork PJ (1999) Somatostatin activation of mitogen-activated protein kinase via somatostatin receptor 1 (SSTR1). Mol Endocrinol 13:24–37CrossRef PubMed
  20.Lahlou H, Saint-Laurent N, Esteve JP, Eychene A, Pradayrol L, Pyronnet S, Susini C (2003) sst2 Somatostatin receptor inhibits cell proliferation through Ras-, Rap1-, and B-Raf-dependent ERK2 activation. J Biol Chem 278:39356–39371CrossRef PubMed
  21.Zaballos MA, García B, Santisteban P (2008) Gbetagamma dimers released in response to thyrotropin activate phosphoinositide 3-kinase and regulate gene expression in thyroid cells. Mol Endocrinol 22:1183–1199CrossRef PubMed
  22.García B, Santisteban P (2002) PI3K is involved in the IGF-I inhibition of TSH-induced sodium/iodide symporter gene expression. Mol Endocrinol 16:342–352CrossRef PubMed
  23.de Rooij JL, Bos J (1997) Minimal Ras-binding domain of Raf1 can be used as an activation-specific probe for Ras. Oncogene 14:623–625CrossRef PubMed
  24.Crespo P, Cachero TG, Xu N, Gutkind JS (1995) Dual effect of beta-adrenergic receptors on mitogen-activated protein kinase. Evidence for a beta gamma-dependent activation and a G alpha s-cAMP-mediated inhibition. J Biol Chem 270:25259–25265CrossRef PubMed
  25.Avidor-Reiss T, Nevo I, Levy R, Pfeuffer T, Vogel Z (1996) Chronic opioid treatment induces adenylyl cyclase V superactivation. Involvement of Gbetagamma. J Biol Chem 271:21309–21315CrossRef PubMed
  26.Obara Y, Okano Y, Ono S, Yamauchi A, Hoshino T, Kurose H, Nakahata N (2008) Betagamma subunits of G(i/o) suppress EGF-induced ERK5 phosphorylation, whereas ERK1/2 phosphorylation is enhanced. Cell Signal 20:1275–1283CrossRef PubMed
  27.Knauf JA, Kuroda H, Basu S, Fagin JA (2003) RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase. Oncogene 22:4406–4412CrossRef PubMed
  28.Xing M (2007) BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev 28:742–762CrossRef PubMed
  29.Riesco-Eizaguirre G, Gutiérrez-Martínez P, García-Cabezas MA, Nistal N, Santisteban P (2006) The oncogene BRAFV600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane. Endocr Relat Cancer 13:257–269CrossRef PubMed
  30.Liu YY, Zhang X, Ringel MD, Jhiang SM (2012) Modulation of sodium iodide symporter expression and function by LY294002, Akti-1/2 and Rapamycin in thyroid cells. Endocr Relat Cancer 19:204–291
  31.Reusch HP, Schaefer M, Plum C, Schultz G, Paul M (2001) Gbeta gamma mediate differentiation of vascular smooth muscle cells. J Biol Chem 276:19540–19547CrossRef PubMed
  32.Guan J, Luo Y, Denker BM (2005) Purkinje cell protein-2 (Pcp2) stimulates differentiation in PC12 cells by Gbetagamma-mediated activation of Ras and p38 MAPK. Biochem J 392:389–397PubMedCentral CrossRef PubMed
  
• 作者单位：Francisco J. Rodríguez-Álvarez (1)
  Eva Jiménez-Mora (1)
  María Caballero (1)
  Beatriz Gallego (1)
  Antonio Chiloeches (1)
  Mª José Toro (1)
  
  1. Departamento de Biología de Sistemas, Unidad Bioquímica y Biología Molecular. Facultad de Medicina, Universidad de Alcalá, Ctra. Madrid-Barcelona Km.33,6, 28871, Alcalá de Henares, Madrid, Spain
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Medical Biochemistry
  Oncology
  Cardiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4919

文摘

Somatostatin (SST) is one of the main regulators of thyroid function. It acts by binding to its receptors, which lead to the dissociation of G proteins into Gαi and Gβγ subunits. However, much less is known about the function of Gβγ in thyroid cells. Here, we studied the role of SST and Gβγ dimers released upon SST stimulation on the Ras-ERK1/2 pathway in FTRL-5 thyroid cells. We demonstrate that SST activates Ras through Gi proteins, since SST-induced Ras activation is inhibited by pertussis toxin. Moreover, the specific sequestration of Gβγ dimers decreases Ras-GTP and phosphorylated ERK1/2 levels, and overexpression of Gβγ increases ERK1/2 phosphorylation induced by SST, indicating that Gβγ dimers released after SST treatment mediate activation of Ras and ERK1/2. On the other hand, SST treatment does not modify the expression of the thyroid differentiation marker sodium/iodide symporter (NIS) through ERK1/2 activation. However, SST increases AKT activation and the inhibition of the Src/PI3K/AKT pathway increases NIS levels in SST-treated cells. Thus, we conclude that, in thyroid cells, signalling from SST receptors to ERK1/2 involves a Gβγ-mediated signal acting on a Ras-dependent pathway. Moreover, we demonstrate that SST might regulates NIS expression through a Src/PI3K/AKT-dependent mechanism, but not through ERK1/2 signalling, showing the main role of this hormone in thyroid function. Keywords Thyroid Somatostatin Gi proteins Gβγ Ras ERK1/2