Gonadotrophin-Releasing Hormone Signalling Downstream of Calmodulin

Journal of Neuroendocrinology

Volumn 24, Issue 12, 2012, Pages 1463-1475

  Melamed, P ^a   Savulescu, D ^b   Lim, S ^a   Wijeweera, A ^b   Luo, Z ^a   Luo, M ^a,c   Pnueli, L ^b,d  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^c STOWERS INSTITUTE FOR MEDICAL RESEARCH   (United States)

^d CENTER FOR CELL AND GENE THERAPY   (United States)

Author keywords

Calcineurin; Calmodulin; CaMK; GnRH; Gonadotroph; Gonadotrophin

Indexed keywords

CALCINEURIN; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE I; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; CALMODULIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; FOCAL ADHESION KINASE; GLYCOGEN SYNTHASE KINASE 3; GONADORELIN; GONADOTROPIN; GUANINE NUCLEOTIDE BINDING PROTEIN; HISTONE DEACETYLASE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; PEPTIDYLPROLYL ISOMERASE PIN1; PROTEIN GEM; RGS2 PROTEIN; TRANCRIPTION FACTOR NUCLEAR FACTOR OF ACTIVATED T CELLS 1; TRANCRIPTION FACTOR NUCLEAR FACTOR OF ACTIVATED T CELLS 2; TRANCRIPTION FACTOR NUCLEAR FACTOR OF ACTIVATED T CELLS 4; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR NFAT3; UNCLASSIFIED DRUG;

CALCIUM CELL LEVEL; CELL CYCLE; CELL PROLIFERATION; CELL STRUCTURE; CYTOSOL; DOWNSTREAM PROCESSING; ENDOPLASMIC RETICULUM; GENE EXPRESSION; GONADOTROPIN SECRETING CELL; HUMAN; INTRACELLULAR SIGNALING; NEGATIVE FEEDBACK; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; REVIEW;

ANIMALS; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES; CALMODULIN; GENE EXPRESSION REGULATION; GONADOTROPHS; GONADOTROPIN-RELEASING HORMONE; GONADOTROPINS; HUMANS; MODELS, BIOLOGICAL; SIGNAL TRANSDUCTION;

EID: 84869801965     PISSN: 09538194     EISSN: 13652826     Source Type: Journal    
DOI: 10.1111/j.1365-2826.2012.02359.x     Document Type: Review

References (133)

1. Miles LE, Hanyaloglu AC, Dromey JR, Pfleger KD, Eidne KA. Gonadotropin-releasing hormone receptor-mediated growth suppression of immortalized LβT2 gonadotrope and stable HEK293 cell lines. Endocrinology 2004; 145: 194-204.
2. Luo M, Koh M, Feng J, Wu Q, Melamed P. Cross-talk in hormonally-regulated gene transcription through induction of estrogen receptor ubiquitylation. Mol Cell Biol 2005; 25: 7386-7398.
3. Melamed P, Abdul Kadir MN, Wijeweera A, Seah S. Transcription of gonadotropin β subunit genes involves cross-talk between the transcription factors and co-regulators that mediate actions of the regulatory hormones. Mol Cell Endocrinol 2006a; 252: 167-183.
4. Zhang H, Bailey JS, Coss D, Lin B, Tsutsumi R, Lawson MA, Mellon PL, Webster NJG. Activin modulates the transcriptional response of LβT2 cells to gonadotropin-releasing hormone and alters cellular proliferation. Mol Endocrinol 2006; 20: 2909-2930.
5. Navratil AM, Knoll JG, Whitesell JD, Tobet SA, Clay CM. Neuroendocrine plasticity in the anterior pituitary: gonadotropin-releasing hormone-mediated movement in vitro and in vivo. Endocrinology 2007; 148: 1736-1744.
6. Feng J, Lawson MA, Melamed P. A proteomic comparison of immature and mature mouse gonadotropes reveals novel differentially expressed nuclear proteins that regulate gonadotropin gene transcription and RNA splicing. Biol Reprod 2008; 79: 546-561.
7. Burger LL, Haisenleder DJ, Dalkin AC, Marshall JC. Regulation of gonadotropin subunit gene transcription. J Mol Endocrinol 2004; 33: 559-584.
8. Ferris HA, Shupnik MA. Mechanisms for pulsatile regulation of the gonadotropin subunit genes by GnRH1. Biol Reprod 2006; 74: 993-998.
9. Burger LL, Haisenleder DJ, Aylor KW, Marshall JC. Regulation of intracellular signaling cascades by GnRH pulse frequency in the rat pituitary: roles for CaMK II, ERK, and JNK activation. Biol Reprod 2008; 79: 947-953.
10. Lim S, Pnueli L, Tan JH, Naor Z, Rajagopal G, Melamed P. Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency. PLoS ONE 2009; 4: e7244.
11. Plant TM, Gay VL, Marshall GR, Arslan M. Puberty in monkeys is triggered by chemical stimulation of the hypothalamus. Proc Natl Acad Sci U S A 1989; 86: 2506-2510.
12. Naor Z. Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor. Front Neuroendocrinol 2009; 30: 10-29.
13. Bliss SP, Navratil AM, Xie JJ, Roberson MS. GnRH signaling, the gonadotrope and endocrine control of fertility. Front Neuroendocrinol 2010; 31: 322-340.
14. Stojilkovic SS. Pituitary cell type-specific electrical activity, calcium signaling and secretion. Biol Res 2006; 39: 403-423.
15. Stojilkovic SS, Catt KJ. Novel aspects of GnRH-induced intracellular signaling and secretion in pituitary gonadotrophs. J Neuroendocrinol 1995; 7: 739-757.
16. Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 2000; 1: 11-21.
17. Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 2003; 4: 517-529.
18. Haisenleder DJ, Yasin M, Marshall JC. Gonadotropin subunit and gonadotropin-releasing hormone receptor gene expression are regulated by alterations in the frequency of calcium pulsatile signals. Endocrinology 1997; 138: 5227-5230.
19. Chin D, Means AR. Calmodulin: a prototypical calcium sensor. Trends Cell Biol 2000; 10: 322-328.
20. Means AR. The year in basic science: calmodulin kinase cascades. Mol Endocrinol 2008; 22: 2759-2765.
21. 2+)/calmodulin-dependent protein kinases. Cell Mol Life Sci 2008; 65: 2637-2657.
22. Izumi S, Iwashita M, Makino T, Saito S, Sakamoto S, Takeda Y, Nozawa S. Phorbol ester-induced LH release in pituitary gonadotropes: effects of antagonists of calmodulin and GnRH. Endocrinol Jpn 1991; 38: 195-204.
23. Conn PM, Chafouleas JG, Rogers D, Means AR. Gonadotropin releasing hormone stimulates calmodulin redistribution in rat pituitary. Nature 1981; 292: 264-265.
24. Cesnjaj M, Catt KJ, Stojilkovic SS. Coordinate actions of calcium and protein kinase-C in the expression of primary response genes in pituitary gonadotropes. Endocrinology 1994; 135: 692-701.
25. Kahl CR, Means AR. Regulation of cell cycle progression by calcium/calmodulin-dependent pathways. Endocr Rev 2003; 24: 719-736.
26. Lim S, Luo M, Koh M, Yang M, Abdul Kadir MN, Tan JH, Ye Z, Wang W, Melamed P. Distinct mechanisms involving diverse histone deacetylases repress expression of the two gonadotropin β-subunit genes in immature gonadotropes, and their actions are overcome by GnRH. Mol Cell Biol 2007; 27: 4105-4120.
27. 2+)/calmodulin-dependent protein kinase kinase β by autophosphorylation. Biochemistry 2011; 50: 8193-8201.
28. Green MF, Anderson KA, Means AR. Characterization of the CaMKK β-AMPK signaling complex. Cell Signal 2011; 23: 2005-2012.
29. Andrade J, Quinn J, Rodriguez AL, Shupnik MA. AMPK is a key intermediary in GnRH- and Insulin-stimulated LHβ gene transcription. Endocr Rev 2010; 31: S1175.
30. McKinsey TA, Zhang CL, Lu JR, Olson EN. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 2000; 408: 106-111.
31. McKinsey TA, Zhang CL, Olson EN. Identification of a signal-responsive nuclear export sequence in class II histone deacetylases. Mol Cell Biol 2001; 21: 6312-6321.
32. Verdin E, Dequiedt F, Kasler HG. Class II histone deacetylases: versatile regulators. Trends Genet 2003; 19: 286-293.
33. Melamed P. The role of histone deacetylases in expression of gonadotropin subunit genes. Trends Endocrinol Metab 2008; 19: 25-31.
34. 2+/calmodulin-dependent protein kinase II. J Biol Chem 2001; 276: 3719-3722.
35. 2+ oscillations. Science 1998; 279: 227-230.
36. 2+ oscillations: a simple model. Cell Calcium 2003; 34: 485-497.
37. Haisenleder DJ, Ferris HA, Shupnik MA. The calcium component of gonadotropin-releasing hormone-stimulated luteinizing hormone subunit gene transcription is mediated by calcium/calmodulin-dependent protein kinase type II. Endocrinology 2003; 144: 2409-2416.
38. Haisenleder DJ, Burger LL, Aylor KW, Dalkin AC, Marshall JC. Gonadotropin-releasing hormone stimulation of gonadotropin subunit transcription: evidence for the involvement of calcium/calmodulin-dependent kinase II (Ca/CAMK II) activation in rat pituitaries. Endocrinology 2003; 144: 2768-2774.
39. Krakauer DC, Page KM, Sealfon S. Module dynamics of the GnRH signal transduction network. J Theor Biol 2002; 218: 457-470.
40. Nguyen KA, Intriago RE, Upadhyay HC, Santos SJ, Webster NJ, Lawson MA. Modulation of gonadotropin-releasing hormone-induced extracellular signal-regulated kinase activation by dual-specificity protein phosphatase 1 in LβT2 gonadotropes. Endocrinology 2010; 151: 4882-4893.
41. Lawson MA, Tsutsumi R, Zhang H, Talukdar I, Butler BK, Santos SJ, Mellon PL, Webster NJ. Pulse sensitivity of the luteinizing hormone β promoter is determined by a negative feedback loop involving early growth response-1 and Ngfi-A binding protein 1 and 2. Mol Endocrinol 2007; 21: 1175-1191.
42. Ciccone NA, Xu S, Lacza CT, Carroll RS, Kaiser UB. Frequency-dependent regulation of follicle-stimulating hormone β by pulsatile gonadotropin-releasing hormone is mediated by functional antagonism of bZIP transcription factors. Mol Cell Biol 2010; 30: 1028-1040.
43. Jorgensen JS, Quirk CC, Nilson JH. Multiple and overlapping combinatorial codes orchestrate hormonal responsiveness and dictate cell-specific expression of the genes encoding luteinizing hormone. Endocr Rev 2004; 25: 521-542.
44. Melamed P. Hormonal signaling to FSHβ gene expression. Mol Cell Endocrinol 2010; 314: 204-212.
45. Ely HA, Mellon PL, Coss D. GnRH Induces the c-fos gene via phosphorylation of SRF by the calcium/calmodulin kinase II pathway. Mol Endocrinol 2011; 25: 669-680.
46. Mistry DS, Tsutsumi R, Fernandez M, Sharma S, Cardenas SA, Lawson MA, Webster NJG. Gonadotropin-releasing hormone pulse sensitivity of follicle-stimulating hormone-β gene is mediated by differential expression of positive regulatory activator protein 1 factors and corepressors SKIL and TGIF1. Mol Endocrinol 2011; 25: 1387-1403.
47. Crivici A, Ikura M. Molecular and structural basis of target recognition by calmodulin. Annu Rev Biophys Biomol Struct 1995; 24: 85-116.
48. Shen XR, Li HM, Ou Y, Tao WB, Dong A, Kong JL, Ji CN, Yu SN. The secondary structure of calcineurin regulatory region and conformational change induced by calcium/calmodulin binding. J Biol Chem 2008; 283: 11407-11413.
49. Luo ZJ, Wijeweera A, Oh YZ, Liou YC, Melamed P. Pin1 regulates gonadotropin β-subunit gene transcription through facilitating the phosphorylation-dependent ubiquitination of SF-1. Mol Cell Biol 2010; 30: 745-763.
50. Pnueli L, Luo M, Wang S, Naor Z, Melamed P. Calcineurin regulates expression of both subunits of the follicle-stimulating hormone through distinct mechanisms. Mol Cell Biol 2011; 31: 5023-5036.
51. Zhang T, Mulvaney JM, Roberson MS. Activation of mitogen-activated protein kinase phosphatase 2 by gonadotropin-releasing hormone. Mol Cell Endocrinol 2001; 172: 79-89.
52. Wurmbach E, Yuen T, Ebersole BJ, Sealfon SC. Gonadotropin-releasing hormone receptor-coupled gene network organization. J Biol Chem 2001; 276: 47195-47201.
53. Roberson MS, Bliss SP, Xie JJ, Navratil AM, Farmerie TA, Wolfe MW, Clay CM. Gonadotropin-releasing hormone induction of extracellular-signal regulated kinase is blocked by inhibition of calmodulin. Mol Endocrinol 2005; 19: 2412-2423.
54. Armstrong SP, Caunt CJ, Finch AR, McArdle CA. Using automated imaging to interrogate gonadotropin-releasing hormone receptor trafficking and function. Mol Cell Endocrinol 2011; 331: 194-204.
55. Marantz Y, Reiss N, Przedecki F, Naor Z. Involvement of protein phosphatases in gonadotropin-releasing-hormone regulated gonadotropin secretion. Mol Cell Endocrinol 1995; 111: 7-11.
56. Purwana IN, Kanasaki H, Oride A, Miyazaki K. Induction of dual specificity phosphatase 1 (DUSP1) by gonadotropin-releasing hormone (GnRH) and the role for gonadotropin subunit gene expression in mouse pituitary gonadotrope LβT2 cells. Biol Reprod 2010; 82: 352-362.
57. 2+/NFAT signaling pathway decode GnRH pulse frequency? J Biol Chem 2009; 284: 35746-35757.
58. Wu H, Peisley A, Graef IA, Crabtree GR. NFAT signaling and the invention of vertebrates. Trends Cell Biol 2007; 17: 251-260.
59. Mueller MR, Rao A. NFAT, immunity and cancer: a transcription factor comes of age. Nat Rev Immunol 2010; 10: 645-656.
60. Holdstock JG, Aylwin SJB, Burrin JM. Calcium and glycoprotein hormone α-subunit gene expression and secretion in αT3-1 gonadotropes. Mol Endocrinol 1996; 10: 1308-1317.
61. Weck J, Anderson AC, Jenkins S, Fallest PC, Shupnik MA. Divergent and composite gonadotropin-releasing hormone-responsive elements in the rat luteinizing hormone subunit genes. Mol Endcrinol 2000; 14: 472-485.
62. Binder AK, Grammer JC, Herndon MK, Stanton JD, Nilson JH. GnRH regulation of Jun and Atf3 requires calcium, calcineurin, and NFAT. Mol Endocrinol 2012; 26: 873-886.
63. Kakar SS, Winters SJ, Zacharias W, Miller DM, Flynn S. Identification of distinct gene expression profiles associated with treatment of LβT2 cells with gonadotropin-releasing hormone agonist using microarray analysis. Gene 2003; 308: 67-77.
64. Youn HD, Chatila TA, Liu JO. Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis. EMBO J 2000; 19: 4323-4331.
65. Li Y, Lau LF. Adrenocorticotropic hormone regulates the activities of the orphan nuclear receptor Nur77 through modulation of phosphorylation. Endocrinology 1997; 138: 4138-4146.
66. Sohn YC, Kwak E, Na YJ, Lee JW, Lee SK. Silencing mediator of retinoid and thyroid hormone receptors and activating signal cointegrator-2 as transcriptional coregulators of the orphan nuclear receptor Nur77. J Biol Chem 2001; 276: 43734-43739.
67. Kelly SN, McKenna TJ, Young LS. Coregulatory protein-orphan nuclear receptor interactions in the human adrenal cortex. J Endocrinol 2005; 186: 33-42.
68. Amelio AL, Miraglia LJ, Conkright JJ, Mercer BA, Batalov S, Cavett V, Orth AP, Busby J, Hogenesch JB, Conkright MD. A coactivator trap identifies NONO (p54nrb) as a component of the cAMP-signaling pathway. Proc Natl Acad Sci USA 2007; 104: 20314-20319.
69. Canettieri G, Coni S, Della Guardia M, Nocerino V, Antonucci L, Di Magno L, Screaton R, Screpanti I, Giannini G, Gulino A. The coactivator CRTC1 promotes cell proliferation and transformation via AP-1. Proc Natl Acad Sci USA 2009; 106: 1445-1450.
70. Conkright MD, Canettieri G, Screaton R, Guzman E, Miraglia L, Hogenesch JB, Montminy M. TORCs: transducers of regulated CREB activity. Mol Cell 2003; 12: 413-423.
71. Kasper LH, Lerach S, Wang JM, Wu S, Jeevan T, Brindle PK. CBP/p300 double null cells reveal effect of coactivator level and diversity on CREB transactivation. EMBO J 2010; 29: 3660-3672.
72. Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR, Takemori H, Okamoto M, Montminy M. The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 2004; 119: 61-74.
73. Takemori H, Okamoto M. Regulation of CREB-mediated gene expression by salt inducible kinase. J Steroid Biochem Mol Biol 2008; 108: 287-291.
74. Ciccone NA, Lacza CT, Hou MY, Gregory SJ, Kam KY, Xu S, Kaiser UB. A composite element that binds basic helix loop helix and basic leucine zipper transcription factors is important for gonadotropin-releasing hormone regulation of the follicle stimulating hormone β gene. Mol Endocrinol 2008; 22: 1908-1923.
75. Breuillaud L, Halfon O, Magistrett PJ, Pralong FP, Cardinaux JR. Mouse fertility is not dependent on the CREB coactivator Crtc1. Nature Med 2009; 15: 989-990.
76. Eto A, Akita Y, Saido TC, Suzuki K, Kawashima S. The role of the calpain-calpstatin system in thyrotropin releasing hormone-induced selective down-regulation of a protein kinase-C isozyme, nPKC-epsilon, in rat pituitary GH(4)C(1) cells. J Biol Chem 1995; 270: 25115-25120.
77. Lu KP, Zhou XZ. The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease. Nat Rev Mol Cell Biol 2007; 8: 904-916.
78. Liou YC, Zhou XZ, Lu KP. Prolyl isomerase Pin 1 as a molecular switch to determine the fate of phosphoproteins. Trends Biochem Sci 2011; 36: 501-514.
79. Lu PJ, Zhou XZ, Liou YC, Noel JP, Lu KP. Critical role of WW domain phosphorylation in regulating phosphoserine binding activity and Pin1 function. J Biol Chem 2002; 277: 2381-2384.
80. Tremblay JJ, Drouin J. Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with Ptx1 and SF-1 to enhance luteinizing hormone β gene transcription. Mol Cell Biol 1999; 19: 2567-2576.
81. Liu WF, Youn HD, Zhou XZ, Lu KP, Liu JO. Binding and regulation of the transcription factor NFAT by the peptidyl prolyl cis-trans isomerase Pin1. FEBS Let 2001; 496: 105-108.
82. Melamed P, Zhu Y, Tan SH, Xie M, Koh M. Gonadotropin releasing hormone activation of c-jun, but not Egr-1, stimulates transcription of a luteinizing hormone β subunit gene. Endocrinology 2006; 147: 3598-3605.
83. Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Horike N, Yoneda M, Ohno H, Tsuchiya Y, Kamata H, Tahara H, Isobe T, Nishimura F, Katagiri H, Oka Y, Fukushima T, Takahashi SI, Kurihara H, Uchida T, Asanoa T. Pin1 associates with and induces translocation of CRTC2 to the cytosol, thereby suppressing cAMP-responsive element transcriptional activity. J Biol Chem 2010; 285: 33018-33027.
84. Rajbhandari P, Finn G, Solodin NM, Singarapu KK, Sahu SC, Markley JL, Kadunc KJ, Ellison-Zelski SJ, Kariagina A, Haslam SZ, Lu KP, Alarid ET. Regulation of estrogen receptor α N-terminus conformation and function by peptidyl prolyl isomerase. Mol Cell Biol 2012; 32: 445-457.
85. Baksh S, DeCaprio JA, Burakoff SJ. Calcineurin regulation of the mammalian G0/G1 checkpoint element, cyclin dependent kinase 4. Oncogene 2000; 19: 2820-2827.
86. Baksh S, Widlund HR, Frazer-Abel AA, Du J, Fosmire S, Fisher DE, DeCaprio JA, Modiano JF, Burakoff SJ. NFATc2-mediated repression of cyclin-dependent kinase 4 expression. Mol Cell 2002; 10: 1071-1081.
87. Zacchi P, Gostissa M, Uchida T, Salvagno C, Avolio F, Volinia S, Ronai Z, Blandino G, Schneider C, Del Sal G. The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults. Nature 2002; 419: 853-857.
88. Zheng H, You H, Zhou XZ, Murray SA, Uchida T, Wulf G, Gu L, Tang X, Lu KP, Xiao ZX. The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature 2002; 419: 849-853.
89. Liou YC, Ryo A, Huang HK, Lu PJ, Bronson R, Fujimori F, Uchida T, Hunter T, Lu KP. Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes. Proc Natl Acad Sci USA 2002; 99: 1335-1340.
90. Wulf GM, Ryo A, Wulf GG, Lee SW, Niu T, Petkova V, Lu KP. Pin1 is overexpressed in breast cancer and cooperates with Ras signaling in increasing the transcriptional activity of c-Jun towards cyclin D1. EMBO J 2001; 20: 3459-3472.
91. Salisbury TB, Binder AK, Grammer JC, Nilson JH. GnRH-regulated expression of Jun and JUN target genes in gonadotropes requires a functional interaction between TCF/LEF family members and β-catenin. Mol Endocrinol 2009; 23: 402-411.
92. Park JE, Lee JA, Park SG, Lee DH, Kim SJ, Kim HJ, Uchida C, Uchida T, Park BC, Cho S. A critical step for JNK activation: isomerization by the prolyl isomerase Pin1. Cell Death Differ 2012; 19: 153-161.
93. Gardner S, Maudsley S, Millar RP, Pawson AJ. Nuclear stabilization of β-catenin and inactivation of glycogen synthase kinase-3β by gonadotropin-releasing hormone: targeting Wnt signaling in the pituitary gonadotrope. Mol Endocrinol 2007; 21: 3028-3038.
94. 2+ signaling. Cell Mol Life Sci 2005; 62: 2405-2413.
95. Santini MP, Talora C, Seki T, Bolgan L, Dotto GP. Cross talk among calcineurin, Sp1/Sp3, and NFAT in control of p21(WAF1/CIP1) expression in keratinocyte differentiation. Proc Natl Acad Sci USA 2001; 98: 9575-9580.
96. Gafter-Gvili A, Sredni B, Gal R, Gafter U, Kalechman Y. Cyclosporin A-induced hair growth in mice is associated with inhibition of calcineurin-dependent activation of NFAT in follicular keratinocytes. Am J Physiol-Cell Biol 2003; 284: C1593-C1603.
97. Kraus S, Levy G, Hanoch T, Naor Z, Seger R. Gonadotropin-releasing hormone induces apoptosis of prostate cancer cells: role of c-Jun NH2-terminal kinase, protein kinase B, and extracellular signal-regulated kinase pathways. Cancer Res 2004; 64: 5736-5744.
98. Maiti K, Oh DY, Moon JS, Acharjee S, Li JH, Bai DG, Park HS, Lee K, Lee YC, Jung NC, Kim K, Vaudry H, Kwon HB, Seong JY. Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death. J Clin Endocrinol Metab 2005; 90: 4287-4298.
99. White CD, Stewart AJ, Lu ZL, Millar RP, Morgan K. Antiproliferative effects of GnRH agonists: prospects and problems for cancer therapy. Neuroendocrinology 2008; 88: 67-79.
100. Wu HM, Cheng JC, Wang HS, Huang HY, MacCalman CD, Leung PC. Gonadotropin-releasing hormone type II induces apoptosis of human endometrial cancer cells by activating GADD45α. Cancer Res 2009; 69: 4202-4208.
101. Mazhawidza W, Winters SJ, Kaiser UB, Kakar SS. Identification.of gene networks modulated by activin in LβT2 cells using DNA microarray analysis. Histol Histopathol 2006; 21: 167-178.
102. Sakai T, Inoue K, Hasegawa Y, Kurosumi K. Effect of passive immunization to gonadotropin-releasing hormone (GnRH) using GnRH antiserum on the mitotic activity of gonadotrophs in castrated male rats. Endocrinology 1988; 122: 2803-2808.
103. Childs GV, Unabia G. Epidermal growth factor and gonadotropin-releasing hormone stimulate proliferation of enriched population of gonadotropes. Endocrinology 2001; 142: 847-853.
104. Lewy H, Ashkenazi IE, Naor Z. Gonadotropin releasing hormone (GnRH) and estradiol (E(2)) regulation of cell cycle in gonadotrophs. Mol Cell Endocrinol 2003; 203: 25-32.
105. Mattson MP, Chan SL. Calcium orchestrates apoptosis. Nat Cell Biol 2003; 5: 1041-1043.
106. Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 2003; 4: 552-565.
107. Clapham DE. Calcium signaling. Cell 2007; 131: 1047-1058.
108. Zhivotovsky B, Orrenius S. Calcium and cell death mechanisms: a perspective from the cell death community. Cell Calcium 2011; 50: 211-221.
109. Cheung LW, Wong AS. Gonadotropin-releasing hormone: GnRH receptor signaling in extrapituitary tissues. FEBS J 2008; 275: 5479-5495.
110. Godoy J, Nishimura M, Webster NJ. Gonadotropin-releasing hormone induces miR-132 and miR-212 to regulate cellular morphology and migration in immortalized LβT2 pituitary gonadotrope cells. Mol Endocrinol 2011; 25: 810-820.
111. Ward Y, Kelly K. Gem protein signaling and regulation. Methods Enzymol 2006; 407: 468-483.
112. Correll RN, Pang C, Niedowicz DM, Finlin BS, Andres DA. The RGK family of GTP-binding proteins: regulators of voltage-dependent calcium channels and cytoskeleton remodeling. Cell Signal 2008; 20: 292-300.
113. 2+ channel expression at the cell surface by the small G-protein kir/Gem. Nature 2001; 411: 701-706.
114. Mahalakshmi RN, Nagashima K, Ng MY, Inagaki N, Hunziker W, Béguin P. Nuclear transport of Kir/Gem requires specific signals and importin α5 and is regulated by calmodulin and predicted serine phosphorylations. Traffic 2007; 8: 1150-1163.
115. Béguin P, Mahalakshmi RN, Nagashima K, Cher DH, Takahashi A, Yamada Y, Seino Y, Hunziker W. 14-3-3 and calmodulin control subcellular distribution of Kir/Gem and its regulation of cell shape and calcium channel activity. J Cell Sci 2005; 118: 1923-1934.
116. q/11. Eur J Pharmacol 2008; 587: 16-24.
117. Fernandez MO, Webster NJG. Regulator of G protein signaling 2 (RGS2) is induced by pulsatile GnRH and alters GnRH-induced gene expression in LβT2 Cells. Endocr Rev 2010; 31: S1924.
118. Willars GB. Mammalian RGS proteins: multifunctional regulators of cellular signalling. Semin Cell Dev Biol 2006; 17: 363-376.
119. Cunningham ML, Waldo GL, Hollinger S, Hepler JR, Harden TK. Protein kinase C phosphorylates RGS2 and modulates its capacity for negative regulation of G α(11) signaling. J Biol Chem 2001; 276: 5438-5444.
120. 2+/calmodulin mediate voltage-dependent control of the G protein cycle in a cardiac K+ channel. Proc Natl Acad Sci USA 2002; 99: 4325-4330.
121. Ishii M, Ikushima M, Kurachi Y. In vivo interaction between RGS4 and calmodulin visualized with FRET techniques: possible involvement of lipid raft. Biochem Biophys Res Commun 2005; 338: 839-846.
122. Nini L, Waheed AA, Panicker LM, Czapiga M, Zhang JH, Simonds WF. R7-binding protein targets the G protein β 5/R7-regulator of G protein signaling complex to lipid rafts in neuronal cells and brain. BMC Biochem 2007; 8: 18.
123. Grabowska D, Jayaraman M, Kaltenbronn KM, Sandiford SL, Wang Q, Jenkins S, Slepak VZ, Smith Y, Blumer KJ. Postnatal induction and localization of R7BP, a membrane-anchoring protein for regulator of G protein signaling 7 family-Gβ5 complexes in brain. Neuroscience 2008; 151: 969-982.
124. Bliss SP, Navratil AM, Breed M, Skinner DC, Clay CM, Roberson MS. Signaling complexes associated with the type I gonadotropin-releasing hormone (GnRH) receptor: colocalization of extracellularly regulated kinase 2 and GnRH receptor within membrane rafts. Mol Endocrinol 2007; 21: 538-549.
125. Maudsley S, Naor Z, Bonfil D, Davidson L, Karali D, Pawson AJ, Larder R, Pope C, Nelson N, Millar RP, Brown P. Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone β-subunit gene. Mol Endocrinol 2007; 21: 1216-1233.
126. Xie JJ, Allen KH, Marguet A, Berghorn KA, Bliss SP, Navratil AM, Guan JL, Roberson MS. Analysis of the calcium-dependent regulation of proline-rich tyrosine kinase 2 by gonadotropin-releasing hormone. Mol Endocrinol 2008; 22: 2322-2335.
127. Dobkin-Bekman M, Naidich M, Rahamim L, Przedecki F, Almog T, Lim S, Melamed P, Liu P, Wohland T, Yao Z, Seger R, Naor Z. A preformed signaling complex mediates GnRH activated ERK phosphorylation of paxillin and FAK at focal adhesions in LβT2 gonadotrope cells. Mol Endocrinol 2009; 23: 1850-1864.
128. Davidson L, Pawson AJ, Millar RP, Maudsley S. Cytoskeletal reorganization dependence of signaling by the gonadotropin releasing hormone receptor. J Biol Chem 2004; 279: 1980-1993.
129. Shen X, Valencia CA, Szostak JW, Dong B, Liu R. Scanning the human proteome for calmodulin-binding proteins. Proc Natl Acad Sci USA 2005; 102: 5969-5974.
130. Berggård T, Arrigoni G, Olsson O, Fex M, Linse S, James P. 140 mouse brain proteins identified by Ca2+-calmodulin affinity chromatography and tandem mass spectrometry. J Proteome Res 2006; 5: 669-687.
131. Saucerman JJ, Bers DM. Calmodulin binding proteins provide domains of local Ca(2+) signaling in cardiac myocytes. J Mol Cell Cardiol 2012; 52: 312-316.
132. Mermelstein PG, Deisseroth K, Dasgupta N, Isaksen AL, Tsien RW. Calmodulin priming: nuclear translocation of a calmodulin complex and the memory of prior neuronal activity. Proc Natl Acad Sci USA 2001; 98: 15342-15347.
133. Shao S, Hegde RS. A calmodulin-dependent translocation pathway for small secretory proteins. Cell 2011; 147: 1576-1588.