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Abstract:

Background Sam68, a member of the signal transduction and activation of RNA metabolism (STAR) family of RNA-binding proteins, has been previously implicated as an adaptor molecule in different signaling systems, including leptin receptor (LEPR) signaling. LEPR activation is known to stimulate JAK-STAT, MAPK and PI3K signaling pathways, thus mediating the biological effects of leptin in different cell types, including trophoblastic cells. We have recently found that leptin stimulation also promotes the overexpression and tyrosine phosphorylation of Sam68 in human trophoblastic JEG-3 cells, suggesting a role for Sam68 in leptin signaling and action in these cells. In the present work, we have studied the participation of Sam68 in the main signaling pathways activated by LEPR to increase growth and proliferation in trophoblastic JEG-3 cells. Methods We used an antisense strategy to down-regulate Sam68 expression in these cells, and we studied LEPR signaling by immunoprecipitation and poly-U affinity precipitation and by analyzing phosphorylation levels of signaling proteins by immunoblot. The effect of leptin on protein synthesis and proliferation was studied by 3[H]-leucine and 3[H]-thymidine incorporation. Results Sam68 knockdown impaired leptin activation of JAK-STAT, PI3K and MAPK signaling pathways in JEG-3 cells. We have also found that leptin-stimulated Sam68 tyrosine phosphorylation is dependent on JAK-2 activity, since the pharmacological inhibitor AG490 prevents the phosphorylation of Sam68 in JEG-3 cells. Finally, the trophic and proliferative effect of leptin in trophoblastic cells is dependent on Sam68 expression, since its down-regulation impaired the leptin-stimulated DNA and protein synthesis. Conclusions These data demonstrate that Sam68 participates in the main signaling pathways of LEPR to mediate the trophic and proliferative effect of leptin in human trophoblastic cells. © 2011 The Author.

Registro:

Documento: Artículo
Título:Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells
Autor:Sánchez-Jiménez, F.; Pérez-Pérez, A.; González-Yanes, C.; Varone, C.L.; Sánchez-Margalet, V.
Filiación:Department of Clinical Biochemistry, Virgen Macarena University Hospital, University of Seville, Av. Dr. Fedriani 3, Seville 41071, Spain
Departamento de Qumica Biolgica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:LEPR signaling; leptin; placenta; Sam68; trophoblast; DNA; Janus kinase 2; leptin; leptin receptor; leucine; mitogen activated protein kinase; phosphatidylinositol 3 kinase; protein Sam68; STAT3 protein; tyrosine; article; cell growth; cell proliferation; controlled study; DNA synthesis; down regulation; enzyme activation; gene overexpression; human; human cell; human cell culture; immunoblotting; immunoprecipitation; protein expression; protein phosphorylation; protein protein interaction; protein synthesis; signal transduction; trophoblast
Año:2011
Volumen:26
Número:9
Página de inicio:2306
Página de fin:2315
DOI: http://dx.doi.org/10.1093/humrep/der187
Título revista:Human Reproduction
Título revista abreviado:Hum. Reprod.
ISSN:02681161
CODEN:HUREE
CAS:DNA, 9007-49-2; leucine, 61-90-5, 7005-03-0; mitogen activated protein kinase, 142243-02-5; phosphatidylinositol 3 kinase, 115926-52-8; tyrosine, 16870-43-2, 55520-40-6, 60-18-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02681161_v26_n9_p2306_SanchezJimenez

Referencias:

  • Babic, I., Cherry, E., Fujita, D.J., SUMO modification of Sam68 enhances its ability to repress cyclin D1 expression and inhibits its ability to induce apoptosis (2006) Oncogene, 25, pp. 4955-4964
  • Banks, A.S., Davis, S.M., Bates, S.H., Myers Jr., M.G., Activation of downstream signals by the long form of the leptin receptor (2000) Journal of Biological Chemistry, 275 (19), pp. 14563-14572. , DOI 10.1074/jbc.275.19.14563
  • Bianchi, E., Barbagallo, F., Valeri, C., Geremia, R., Salustri, A., De Felici, M., Sette, C., Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development (2010) Hum Mol Genet, 19, pp. 4886-4894
  • Busa, R., Paronetto, M.P., Farini, D., Pierantozzi, E., Botti, F., Angelini, D.F., Attisani, F., Sette, C., The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells (2007) Oncogene, 26 (30), pp. 4372-4382. , DOI 10.1038/sj.onc.1210224, PII 1210224
  • Caprio, M., Fabbrini, E., Isidori, A.M., Aversa, A., Fabbri, A., Leptin in reproduction (2001) Trends in Endocrinology and Metabolism, 12 (2), pp. 65-72. , PII S1043276000003520
  • Chakravarti, N., Myers, J.N., Aggarwal, B.B., Targeting constitutive and interleukin-6-inducible signal transducers and activators of transcription 3 pathway in head and neck squamous cell carcinoma cells by curcumin (diferuloylmethane) (2006) International Journal of Cancer, 119 (6), pp. 1268-1275. , DOI 10.1002/ijc.21967
  • Cirillo, D., Rachiglio, A.M., La Montagna, R., Giordano, A., Normanno, N., Leptin signaling in breast cancer: An overview (2008) J Cell Biochem, 105, pp. 956-964
  • Cote, J., Boisvert, F.-M., Boulanger, M.-C., Bedford, M.T., Richard, S., Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1 (2003) Molecular Biology of the Cell, 14 (1), pp. 274-287. , DOI 10.1091/mbc.E02-08-0484
  • Cross, D.A.E., Alessi, D.R., Cohen, P., Andjelkovich, M., Hemmings, B.A., Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B (1995) Nature, 378 (6559), pp. 785-789. , DOI 10.1038/378785a0
  • Derry, J.J., Richard, S., Carvajal, H.V., Ye, X., Vasioukhin, V., Cochrane, A.W., Chen, T., Tyner, A.L., Sik (BRK) phosphorylates sam68 in the nucleus and negatively regulates Its RNA binding ability (2000) Molecular and Cellular Biology, 20 (16), pp. 6114-6126. , DOI 10.1128/MCB.20.16.6114-6126.2000
  • Dotsch, J., Nusken, K.-D., Knerr, I., Kirschbaum, M., Repp, R., Rascher, W., Leptin and neuropeptide Y gene expression in human placenta: Ontogeny and evidence for similarities to hypothalamic regulation (1999) Journal of Clinical Endocrinology and Metabolism, 84 (8), pp. 2755-2758
  • Fruhbeck, G., Intracellular signalling pathways activated by leptin (2006) Biochemical Journal, 393 (1), pp. 7-20. , DOI 10.1042/BJ20051578
  • Fusaki, N., Iwamatsu, A., Iwashima, M., Fujisawa, J.-I., Interaction between Sam68 and Src family tyrosine kinases, Fyn and Lck, in T cell receptor signaling (1997) Journal of Biological Chemistry, 272 (10), pp. 6214-6219. , DOI 10.1074/jbc.272.10.6214
  • Gambino, Y.P., Maymo, J.L., Perez-Perez, A., Duenas, J.L., Sanchez-Margalet, V., Calvo, J.C., Varone, C.L., 17Beta-estradiol enhances leptin expression in human placental cells through genomic and nongenomic actions (2010) Biol Reprod, 83, pp. 42-51
  • Gao, J., Tian, J., Lv, Y., Shi, F., Kong, F., Shi, H., Zhao, L., Leptin induces functional activation of cyclooxygenase-2 through JAK2/STAT3, MAPK/ERK, and PI3K/AKT pathways in human endometrial cancer cells (2009) Cancer Sci, 100, pp. 389-395
  • Ghilardi, N., Skoda, R.C., The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line (1997) Molecular Endocrinology, 11 (4), pp. 393-399. , DOI 10.1210/me.11.4.393
  • Henson, M.C., Castracane, V.D., Leptin in pregnancy: An update (2006) Biology of Reproduction, 74 (2), pp. 218-229. , DOI 10.1095/biolreprod.105.045120
  • Jaffe, T., Schwartz, B., Leptin promotes motility and invasiveness in human colon cancer cells by activating multiple signal-transduction pathways (2008) Int J Cancer, 123, pp. 2543-2556
  • Jiang, L., Li, Z., Rui, L., Leptin stimulates both JAK2-dependent and JAK2-independent signaling pathways (2008) J Biol Chem, 283, pp. 28066-28073
  • Kloek, C., Haq, A.K., Dunn, S.L., Lavery, H.J., Banks, A.S., Myers Jr., M.G., Regulation of Jak kinases by intracellular leptin receptor sequences (2002) Journal of Biological Chemistry, 277 (44), pp. 41547-41555. , DOI 10.1074/jbc.M205148200
  • Lang, V., Mege, D., Semichon, M., Gary-Gouy, H., Bismuth, G., A dual participation of ZAP-70 and scr protein tyrosine kinases is required for TCR-induced tyrosine phosphorylation of sam68 in jurkat T cells (1997) European Journal of Immunology, 27 (12), pp. 3360-3367. , DOI 10.1002/eji.1830271235
  • Lukong, K.E., Larocque, D., Tyner, A.L., Richard, S., Tyrosine phosphorylation of Sam68 by breast tumor kinase regulates intranuclear localization and cell cycle progression (2005) Journal of Biological Chemistry, 280 (46), pp. 38639-38647. , http://www.jbc.org/cgi/reprint/280/46/38639, DOI 10.1074/jbc.M505802200
  • Magarinos, M.P., Sanchez-Margalet, V., Kotler, M., Calvo, J.C., Varone, C.L., Leptin promotes cell proliferation and survival of trophoblastic cells (2007) Biology of Reproduction, 76 (2), pp. 203-210. , DOI 10.1095/biolreprod.106.051391
  • Maroni, P., Citterio, L., Piccoletti, R., Bendinelli, P., Sam68 and ERKs regulate leptin-induced expression of OB-Rb mRNA in C2C12 myotubes (2009) Mol Cell Endocrinol, 309, pp. 26-31
  • Martin-Romero, C., Sanchez-Margalet, V., Human leptin activates PI3K and MAPK pathways in human peripheral blood mononuclear cells: Possible role of Sam68 (2001) Cellular Immunology, 212 (2), pp. 83-91. , DOI 10.1006/cimm.2001.1851
  • Masuzaki, H., Ogawa, Y., Sagawa, N., Hosoda, K., Matsumoto, T., Mise, H., Nishimura, H., Nakao, K., Nonadipose tissue production of leptin: Leptin as a novel placenta- derived hormone in humans (1997) Nature Medicine, 3 (9), pp. 1029-1033. , DOI 10.1038/nm0997-1029
  • Matter, N., Herrlich, P., Konig, H., Signal-dependent regulation of splicing via phosphorylation of Sam68 (2002) Nature, 420 (6916), pp. 691-695. , DOI 10.1038/nature01153
  • Mauvoisin, D., Prevost, M., Ducheix, S., Arnaud, M.P., Mounier, C., Key role of the ERK1/2 MAPK pathway in the transcriptional regulation of the Stearoyl-CoA Desaturase (SCD1) gene expression in response to leptin (2010) Mol Cell Endocrinol, 319, pp. 116-128
  • Maymo, J.L., Perez Perez, A., Sanchez-Margalet, V., Duenas, J.L., Calvo, J.C., Varone, C.L., Up-regulation of placental leptin by human chorionic gonadotropin (2009) Endocrinology, 150, pp. 304-313
  • Maymo, J.L., Perez Perez, A., Duenas, J.L., Calvo, J.C., Sanchez-Margalet, V., Varone, C.L., Regulation of placental leptin expression by cyclic adenosine 5 ′-monophosphate involves cross talk between protein kinase A and mitogen-activated protein kinase signaling pathways (2010) Endocrinology, 151, pp. 3738-3751
  • Myers Jr., M.G., Leptin receptor signaling and the regulation of mammalian physiology (2004) Recent Prog Horm Res, 59, pp. 287-304
  • Myers, M.G., Cowley, M.A., Munzberg, H., Mechanisms of leptin action and leptin resistance (2008) Annual Review of Physiology, 70, pp. 537-556. , DOI 10.1146/annurev.physiol.70.113006.100707
  • Najib, S., Sanchez-Margalet, V., Sam68 associates with the SH3 domains of Grb2 recruiting GAP to the Grb2-SOS complex in insulin receptor signaling (2002) J Cell Biochem, 86, pp. 99-106
  • Najib, S., Martin-Romero, C., Gonzalez-Yanes, C., Sanchez-Margalet, V., Role of Sam68 as an adaptor protein in signal transduction (2005) Cellular and Molecular Life Sciences, 62 (1), pp. 36-43. , DOI 10.1007/s00018-004-4309-3
  • O'Rourke, L., Shepherd, P.R., Biphasic regulation of extracellular-signal-regulated protein kinase by leptin in macrophages: Role in regulating STAT3 Ser727 phosphorylation and DNA binding (2002) Biochemical Journal, 364 (3), pp. 875-879. , DOI 10.1042/BJ20020295
  • Paronetto, M.P., Zalfa, F., Botti, F., Geremia, R., Bagni, C., Sette, C., The nuclear RNA-binding protein Sam68 translocates to the cytoplasm and associates with the polysemes in mouse spermatocytes (2006) Molecular Biology of the Cell, 17 (1), pp. 14-24. , DOI 10.1091/mbc.E05-06-0548
  • Paronetto, M.P., Achsel, T., Massiello, A., Chalfant, C.E., Sette, C., The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x (2007) Journal of Cell Biology, 176 (7), pp. 929-939. , http://www.jcb.org/cgi/reprint/176/7/929, DOI 10.1083/jcb.200701005
  • Paronetto, M.P., Bianchi, E., Geremia, R., Sette, C., Dynamic expression of the RNA-binding protein Sam68 during mouse pre-implantation development (2008) Gene Expr Patterns, 8, pp. 311-322
  • Paronetto, M.P., Messina, V., Bianchi, E., Barchi, M., Vogel, G., Moretti, C., Palombi, F., Richard, S., Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis (2009) J Cell Biol, 185, pp. 235-249
  • Paronetto, M.P., Cappellari, M., Busa, R., Pedrotti, S., Vitali, R., Comstock, C., Hyslop, T., Sette, C., Alternative splicing of the cyclin D1 proto-oncogene is regulated by the RNA-binding protein Sam68 (2010) Cancer Res, 70, pp. 229-239
  • Perez-Perez, A., Maymo, J., Duenas, J.L., Goberna, R., Calvo, J.C., Varone, C., Sanchez-Margalet, V., Leptin prevents apoptosis of trophoblastic cells by activation of MAPK pathway (2008) Arch Biochem Biophys, 477, pp. 390-395
  • Perez-Perez, A., Maymo, J., Gambino, Y., Duenas, J.L., Goberna, R., Varone, C., Sanchez-Margalet, V., Leptin stimulates protein synthesis-activating translation machinery in human trophoblastic cells (2009) Biol Reprod, 81, pp. 826-832
  • Perez-Perez, A., Gambino, Y., Maymo, J., Goberna, R., Fabiani, F., Varone, C., Sanchez-Margalet, V., MAPK and PI3K activities are required for leptin stimulation of protein synthesis in human trophoblastic cells (2010) Biochem Biophys Res Commun, 396, pp. 956-960
  • Rho, J., Choi, S., Jung, C.-R., Im, D.-S., Arginine methylation of Sam68 and SLM proteins negatively regulates their poly(U) RNA binding activity (2007) Archives of Biochemistry and Biophysics, 466 (1), pp. 49-57. , DOI 10.1016/j.abb.2007.07.017, PII S0003986107003761
  • Richard, S., Yu, D., Blumer, K.J., Hausladen, D., Olszowy, M.W., Connelly, P.A., Shaw, A.S., Association of p62, a multifunctional SH2-and SH3-domain-binding protein, with src family tyrosine kinases, Grb2, and phospholipase C gamma-1 (1995) Mol Cell Biol, 15, pp. 186-197
  • Richard, S., Torabi, N., Franco, G.V., Tremblay, G.A., Chen, T., Vogel, G., Morel, M., Komarova, S., Ablation of the Sam68 RNA binding protein protects mice from age-related bone loss (2005) PLoS Genet, 1, pp. e74
  • Richard, S., Vogel, G., Huot, M.E., Guo, T., Muller, W.J., Lukong, K.E., Sam68 haploinsufficiency delays onset of mammary tumorigenesis and metastasis (2008) Oncogene, 27, pp. 548-556
  • Sanchez-Jimenez, F., Perez-Perez, A., Gonzalez-Yanes, C., Najib, S., Varone, C.L., Sanchez-Margalet, V., Leptin receptor activation increases Sam68 tyrosine phosphorylation and expression in human trophoblastic cells (2011) Mol Cell Endocrinol, 332, pp. 221-227
  • Sanchez-Margalet, V., Martin-Romero, C., Human leptin signaling in human peripheral blood mononuclear cells: Activation of the JAK-STAT pathway (2001) Cellular Immunology, 211 (1), pp. 30-36. , DOI 10.1006/cimm.2001.1815
  • Sanchez-Margalet, V., Najib, S., P68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K (1999) FEBS Letters, 455 (3), pp. 307-310. , DOI 10.1016/S0014-5793(99)00887-X, PII S001457939900887X
  • Sanchez-Margalet, V., Najib, S., Sam68 is a docking protein linking GAP and PI3K in insulin receptor signaling (2001) Molecular and Cellular Endocrinology, 183 (1-2), pp. 113-121. , DOI 10.1016/S0303-7207(01)00587-1, PII S0303720701005871
  • Sanchez-Margalet, V., Goldfine, I.D., Truitt, K., Imboden, J., Sung, C.K., Role of p85 subunit of phosphatidylinositol-3-kinase as an adaptor molecule linking the insulin receptor to insulin receptor substrate 1 (1995) Mol Endocrinol, 9, pp. 435-442
  • Sanchez-Margalet, V., Gonzalez-Yanes, C., Najib, S., Fernandez-Santos, J.M., Martin-Lacave, I., The expression of Sam68, a protein involved in insulin signal transduction, is enhanced by insulin stimulation (2003) Cellular and Molecular Life Sciences, 60 (4), pp. 751-758. , DOI 10.1007/s00018-003-2342-2
  • Sanchez-Margalet, V., Martin-Romero, C., Santos-Alvarez, J., Goberna, R., Najib, S., Gonzalez-Yanes, C., Role of leptin as an immunomodulator of blood mononuclear cells: Mechanisms of action (2003) Clinical and Experimental Immunology, 133 (1), pp. 11-19. , DOI 10.1046/j.1365-2249.2003.02190.x
  • Schwartz, M.W., Seeley, R.J., Campfield, L.A., Burn, P., Baskin, D.G., Identification of targets of leptin action in rat hypothalamus (1996) Journal of Clinical Investigation, 98 (5), pp. 1101-1106
  • Sette, C., Messina, V., Paronetto, M.P., Sam68: A new STAR in the male fertility firmament (2010) J Androl, 31, pp. 66-74
  • Smith, P.K., Krohn, R.I., Hermanson, G.T., Measurement of protein using bicinchoninic acid (1985) Analytical Biochemistry, 150 (1), pp. 76-85. , DOI 10.1016/0003-2697(85)90442-7
  • Wang, L.L., Richard, S., Shaw, A.S., P62 association with RNA is regulated by tyrosine phosphorylation (1995) J Biol Chem, 270, pp. 2010-2013
  • Wang, L.H., Kirken, R.A., Erwin, R.A., Yu, C.-R., Farrar, W.L., JAK3, STAT, and MAPK signaling pathways as novel molecular targets for the tyrphostin AG-490 regulation of IL-2-mediated T cell response (1999) Journal of Immunology, 162 (7), pp. 3897-3904
  • Zhang, M., Guller, S., Huang, Y., Method to Enhance Transfection Efficiency of Cell Lines and Placental Fibroblasts (2007) Placenta, 28 (8-9), pp. 779-782. , DOI 10.1016/j.placenta.2007.01.012, PII S0143400407000161

Citas:

---------- APA ----------
Sánchez-Jiménez, F., Pérez-Pérez, A., González-Yanes, C., Varone, C.L. & Sánchez-Margalet, V. (2011) . Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells. Human Reproduction, 26(9), 2306-2315.
http://dx.doi.org/10.1093/humrep/der187
---------- CHICAGO ----------
Sánchez-Jiménez, F., Pérez-Pérez, A., González-Yanes, C., Varone, C.L., Sánchez-Margalet, V. "Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells" . Human Reproduction 26, no. 9 (2011) : 2306-2315.
http://dx.doi.org/10.1093/humrep/der187
---------- MLA ----------
Sánchez-Jiménez, F., Pérez-Pérez, A., González-Yanes, C., Varone, C.L., Sánchez-Margalet, V. "Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells" . Human Reproduction, vol. 26, no. 9, 2011, pp. 2306-2315.
http://dx.doi.org/10.1093/humrep/der187
---------- VANCOUVER ----------
Sánchez-Jiménez, F., Pérez-Pérez, A., González-Yanes, C., Varone, C.L., Sánchez-Margalet, V. Sam68 mediates leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic JEG-3 cells. Hum. Reprod. 2011;26(9):2306-2315.
http://dx.doi.org/10.1093/humrep/der187