Protein Kinase A: A Master Kinase of Granulosa Cell Differentiation

被引:50
作者
Puri, Pawan [1 ]
Little-Ihrig, Lynda [1 ]
Chandran, Uma [2 ]
Law, Nathan C. [3 ]
Hunzicker-Dunn, Mary [3 ]
Zeleznik, Anthony J. [1 ]
机构
[1] Univ Pittsburgh, Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15206 USA
[3] Washington State Univ, Coll Vet Med, Sch Mol Biosci, Pullman, WA 99164 USA
来源
SCIENTIFIC REPORTS | 2016年 / 6卷
关键词
FOLLICLE-STIMULATING-HORMONE; ELEMENT-BINDING PROTEIN; GROWTH-FACTOR RECEPTOR; GENE-EXPRESSION; AROMATASE GENE; HIPPO PATHWAY; FACTOR-I; ACTIVATION; RAT; FSH;
D O I
10.1038/srep28132
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Activation of protein kinase A (PKA) by follicle stimulating hormone (FSH) transduces the signal that drives differentiation of ovarian granulosa cells (GCs). An unresolved question is whether PKA is sufficient to initiate the complex program of GC responses to FSH. We compared signaling pathways and gene expression profiles of GCs stimulated with FSH or expressing PKA-CQR, a constitutively active mutant of PKA. Both FSH and PKA-CQR stimulated the phosphorylation of proteins known to be involved in GC differentiation including CREB, beta-catenin, AKT, p42/44 MAPK, GAB2, GSK-3 beta, FOXO1, and YAP. In contrast, FSH stimulated the phosphorylation of p38 MAP kinase but PKA-CQR did not. Microarray analysis revealed that 85% of transcripts that were up-regulated by FSH were increased to a comparable extent by PKA-CQR and of the transcripts that were down-regulated by FSH, 76% were also down-regulated by PKA-CQR. Transcripts regulated similarly by FSH and PKA-CQR are involved in steroidogenesis and differentiation, while transcripts more robustly up-regulated by PKA-CQR are involved in ovulation. Thus, PKA, under the conditions of our experimental approach appears to function as a master upstream kinase that is sufficient to initiate the complex pattern of intracellular signaling pathway and gene expression profiles that accompany GC differentiation.
引用
收藏
页数:12
相关论文
共 49 条
[1]   Follicle-stimulating hormone activation of hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follicular differentiation [J].
Alam, H ;
Maizels, ET ;
Park, Y ;
Ghaey, S ;
Feiger, ZJ ;
Chandel, NS ;
Hunzicker-Dunn, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (19) :19431-19440
[2]   A delayed gonadotropin-dependent and growth factor-mediated activation of the extracellular signal-regulated kinase 1/2 cascade negatively regulates aromatase expression in granulosa cells [J].
Andric, Nebojsa ;
Ascoli, Mario .
MOLECULAR ENDOCRINOLOGY, 2006, 20 (12) :3308-3320
[3]   GATA4 and GATA6 Silencing in Ovarian Granulosa Cells Affects Levels of mRNAs Involved in Steroidogenesis, Extracellular Structure Organization, IGF-I Activity, and Apoptosis [J].
Bennett, Jill ;
Baumgarten, Sarah C. ;
Stocco, Carlos .
ENDOCRINOLOGY, 2013, 154 (12) :4845-4858
[4]   Loss of GATA-6 and GATA-4 in Granulosa Cells Blocks Folliculogenesis, Ovulation, and Follicle Stimulating Hormone Receptor Expression Leading to Female Infertility [J].
Bennett, Jill ;
Wu, Yan-Guang ;
Gossen, Jan ;
Zhou, Ping ;
Stocco, Carlos .
ENDOCRINOLOGY, 2012, 153 (05) :2474-2485
[5]   Targeting protein-protein interactions in complexes organized by A kinase anchoring proteins [J].
Calejo, Ana I. ;
Tasken, Kjetil .
FRONTIERS IN PHARMACOLOGY, 2015, 6
[6]  
Carlone DL, 1997, J STEROID BIOCHEM, V61, P223, DOI 10.1016/S0960-0760(97)80016-7
[7]   Identification of cAMP-dependent protein kinase holoenzymes in preantral- and preovulatory-follicle-enriched ovaries, and their association with A-kinase-anchoring proteins [J].
Carr, DW ;
Cutler, RE ;
Cottom, JE ;
Salvador, LM ;
Fraser, IDC ;
Scott, JD ;
Hunzicker-Dunn, M .
BIOCHEMICAL JOURNAL, 1999, 344 :613-623
[8]   Follicle-stimulating hormone activates extracellular signal-regulated kinase but not extracellular signal-regulated kinase kinase through a 100-kDa phosphotyrosine phosphatase [J].
Cottom, J ;
Salvador, LM ;
Maizels, ET ;
Reierstad, S ;
Park, Y ;
Carr, DW ;
Davare, MA ;
Hell, JW ;
Palmer, SS ;
Dent, P ;
Kawakatsu, H ;
Ogata, M ;
Hunzicker-Dunn, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (09) :7167-7179
[9]   Specificity and mechanism of action of some commonly used protein kinase inhibitors [J].
Davies, SP ;
Reddy, H ;
Caivano, M ;
Cohen, P .
BIOCHEMICAL JOURNAL, 2000, 351 (351) :95-105
[10]  
Donaubauer E.M., 2016, The Journal of biological chemistry