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New Signaling Pathways for Hormones and Cyclic Adenosine 3',5'-Monophosphate Action in Endocrine Cells

Department of Molecular and Cellular Biology Baylor College of Medicine Houston, Texas 77030

The glycoprotein hormones, ACTH, TSH, FSH, and LH regulate diverse functions in endocrine cells. Although cAMP and PKA have long been shown to mediate specific intracellular signaling events including the transcription of specific genes via the CREB-CBP complex, recent observations have indicated that PKA does not account for all of the intracellular targets of cAMP. For example, TSH stimulation of thyroid cell proliferation is not completely blocked by PKA inhibitors. TSH and FSH can stimulate PKB phosphorylation by a PKAindependent but PI3-K/PDK1-dependent pathway. An FSH inducible kinase, Sgk, has recently been shown to be a close relative of PKB. Sgk is also a target of PI3-K-PDK1 pathway, indicating that some effects previously ascribed to PKB may be mediated by this inducible kinase. The identification of novel cAMP-binding proteins that exhibit guanine nucleotide exchange (GEF) activity (cAMP-GEFS; Epacs) has open new doors for cAMP action that include activation of small GTPases such as Rap1a, Rap2, and possibly Ras. These GTPases are known activators of downstream kinase cascades, including p38MAPK and Erk1/2 as well as PI3-K. Thus, FSH and TSH activation of PKB and Sgk may occur via this alternative cAMP pathway that involves cAMP-GEFs and the activation of the PI3-K/PDK1 pathway.

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				O. Dohan, A. De la Vieja, V. Paroder, C. Riedel, M. Artani, M. Reed, C. S. Ginter, and N. Carrasco The Sodium/Iodide Symporter (NIS): Characterization, Regulation, and Medical Significance Endocr. Rev., February 1, 2003; 24(1): 48 - 77. [Abstract] [Full Text] [PDF]

				Y. Wang and W. Ge Involvement of Cyclic Adenosine 3',5'-Monophosphate in the Differential Regulation of Activin {beta}A and {beta}B Expression by Gonadotropin in the Zebrafish Ovarian Follicle Cells Endocrinology, February 1, 2003; 144(2): 491 - 499. [Abstract] [Full Text] [PDF]

				R. M. Rao, Y. Jo, S. Leers-Sucheta, H. S. Bose, W. L. Miller, S. Azhar, and D. M. Stocco Differential Regulation of Steroid Hormone Biosynthesis in R2C and MA-10 Leydig Tumor Cells: Role of SR-B1-Mediated Selective Cholesteryl Ester Transport Biol Reprod, January 1, 2003; 68(1): 114 - 121. [Abstract] [Full Text] [PDF]

				G. W. Pearson and M. H. Cobb Cell Condition-dependent Regulation of ERK5 by cAMP J. Biol. Chem., December 6, 2002; 277(50): 48094 - 48098. [Abstract] [Full Text] [PDF]

				D. J. McLean, P. J. Friel, D. Pouchnik, and M. D. Griswold Oligonucleotide Microarray Analysis of Gene Expression in Follicle-Stimulating Hormone-Treated Rat Sertoli Cells Mol. Endocrinol., December 1, 2002; 16(12): 2780 - 2792. [Abstract] [Full Text] [PDF]

				M. Nakazaki, A. Crane, M. Hu, V. Seghers, S. Ullrich, L. Aguilar-Bryan, and J. Bryan cAMP-Activated Protein Kinase-Independent Potentiation of Insulin Secretion by cAMP Is Impaired in SUR1 Null Islets Diabetes, December 1, 2002; 51(12): 3440 - 3449. [Abstract] [Full Text] [PDF]

				T. Kagawa, L. Varticovski, Y. Sai, and I. M. Arias Mechanism by which cAMP activates PI3-kinase and increases bile acid secretion in WIF-B9 cells Am J Physiol Cell Physiol, December 1, 2002; 283(6): C1655 - C1666. [Abstract] [Full Text] [PDF]

				J. Liu, T. Vanttinen, C. Hyden-Granskog, and R. Voutilainen Regulation of follistatin-related gene (FLRG) expression by protein kinase C and prostaglandin E2 in cultured granulosa-luteal cells Mol. Hum. Reprod., November 1, 2002; 8(11): 992 - 997. [Abstract] [Full Text] [PDF]

				H. Takemori, Y. Katoh, N. Horike, J. Doi, and M. Okamoto ACTH-induced Nucleocytoplasmic Translocation of Salt-inducible Kinase. IMPLICATION IN THE PROTEIN KINASE A-ACTIVATED GENE TRANSCRIPTION IN MOUSE ADRENOCORTICAL TUMOR CELLS J. Biol. Chem., October 25, 2002; 277(44): 42334 - 42343. [Abstract] [Full Text] [PDF]

				M. Desclozeaux, I. N. Krylova, F. Horn, R. J. Fletterick, and H. A. Ingraham Phosphorylation and Intramolecular Stabilization of the Ligand Binding Domain in the Nuclear Receptor Steroidogenic Factor 1 Mol. Cell. Biol., October 15, 2002; 22(20): 7193 - 7203. [Abstract] [Full Text] [PDF]

				M. Paciga, A. J. Watson, G. E. DiMattia, and G. F. Wagner Ovarian Stanniocalcin Is Structurally Unique in Mammals and Its Production and Release Are Regulated through the Luteinizing Hormone Receptor Endocrinology, October 1, 2002; 143(10): 3925 - 3934. [Abstract] [Full Text] [PDF]

				J. J. Tremblay, F. Hamel, and R. S. Viger Protein Kinase A-Dependent Cooperation between GATA and CCAAT/Enhancer-Binding Protein Transcription Factors Regulates Steroidogenic Acute Regulatory Protein Promoter Activity Endocrinology, October 1, 2002; 143(10): 3935 - 3945. [Abstract] [Full Text] [PDF]

				K. Taki, T. Kogai, Y. Kanamoto, J. M. Hershman, and G. A. Brent A Thyroid-Specific Far-Upstream Enhancer in the Human Sodium/Iodide Symporter Gene Requires Pax-8 Binding and Cyclic Adenosine 3',5'-Monophosphate Response Element-Like Sequence Binding Proteins for Full Activity and Is Differentially Regulated in Normal and Thyroid Cancer Cells Mol. Endocrinol., October 1, 2002; 16(10): 2266 - 2282. [Abstract] [Full Text] [PDF]

				A. Bell, A. Gagnon, P. Dods, D. Papineau, M. Tiberi, and A. Sorisky TSH signaling and cell survival in 3T3-L1 preadipocytes Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1056 - C1064. [Abstract] [Full Text] [PDF]

				J. A. Ehses, S. L. Pelech, R. A. Pederson, and C. H. S. McIntosh Glucose-dependent Insulinotropic Polypeptide Activates the Raf-Mek1/2-ERK1/2 Module via a Cyclic AMP/cAMP-dependent Protein Kinase/Rap1-mediated Pathway J. Biol. Chem., September 27, 2002; 277(40): 37088 - 37097. [Abstract] [Full Text] [PDF]

				V. M. Laurich, A. M. Trbovich, F. H. O'Neill, C. P. Houk, P. M. Sluss, A. H. Payne, P. K. Donahoe, and J. Teixeira Mullerian Inhibiting Substance Blocks the Protein Kinase A-Induced Expression of Cytochrome P450 17{alpha}-Hydroxylase/C17-20 Lyase mRNA in a Mouse Leydig Cell Line Independent of cAMP Responsive Element Binding Protein Phosphorylation Endocrinology, September 1, 2002; 143(9): 3351 - 3360. [Abstract] [Full Text] [PDF]

				S. Eimerl and J. Orly Regulation of Steroidogenic Genes by Insulin-Like Growth Factor-1 and Follicle-Stimulating Hormone: Differential Responses of Cytochrome P450 Side-Chain Cleavage, Steroidogenic Acute Regulatory Protein, and 3{beta}-Hydroxysteroid Dehydrogenase/Isomerase in Rat Granulosa Cells Biol Reprod, September 1, 2002; 67(3): 900 - 910. [Abstract] [Full Text] [PDF]

				C. R. L. Webster, P. Usechak, and M. S. Anwer cAMP inhibits bile acid-induced apoptosis by blocking caspase activation and cytochrome c release Am J Physiol Gastrointest Liver Physiol, September 1, 2002; 283(3): G727 - G738. [Abstract] [Full Text] [PDF]

				L. Lou, J. Urbani, F. Ribeiro-Neto, and D. L. Altschuler cAMP Inhibition of Akt Is Mediated by Activated and Phosphorylated Rap1b J. Biol. Chem., August 30, 2002; 277(36): 32799 - 32806. [Abstract] [Full Text] [PDF]

				F. Liu, I. Usui, L. G. Evans, D. A. Austin, P. L. Mellon, J. M. Olefsky, and N. J. G. Webster Involvement of Both Gq/11 and Gs Proteins in Gonadotropin-releasing Hormone Receptor-mediated Signaling in Lbeta T2 Cells J. Biol. Chem., August 23, 2002; 277(35): 32099 - 32108. [Abstract] [Full Text] [PDF]

				H.-Y. Kim and Y. Rikihisa Roles of p38 Mitogen-Activated Protein Kinase, NF-{kappa}B, and Protein Kinase C in Proinflammatory Cytokine mRNA Expression by Human Peripheral Blood Leukocytes, Monocytes, and Neutrophils in Response to Anaplasma phagocytophila Infect. Immun., August 1, 2002; 70(8): 4132 - 4141. [Abstract] [Full Text] [PDF]

				T. Kamei, S. R. Jones, B. M. Chapman, K. L. MCGonigle, G. Dai, and M. J. Soares The Phosphatidylinositol 3-Kinase/Akt Signaling Pathway Modulates the Endocrine Differentiation of Trophoblast Cells Mol. Endocrinol., July 1, 2002; 16(7): 1469 - 1481. [Abstract] [Full Text] [PDF]

				D. Kovalovsky, D. Refojo, A. C. Liberman, D. Hochbaum, M. P. Pereda, O. A. Coso, G. K. Stalla, F. Holsboer, and E. Arzt Activation and Induction of NUR77/NURR1 in Corticotrophs by CRH/cAMP: Involvement of Calcium, Protein Kinase A, and MAPK Pathways Mol. Endocrinol., July 1, 2002; 16(7): 1638 - 1651. [Abstract] [Full Text] [PDF]

				J. S. Richards, S. C. Sharma, A. E. Falender, and Y. H. Lo Expression of FKHR, FKHRL1, and AFX Genes in the Rodent Ovary: Evidence for Regulation by IGF-I, Estrogen, and the Gonadotropins Mol. Endocrinol., March 1, 2002; 16(3): 580 - 599. [Abstract] [Full Text] [PDF]