KEGG   PATHWAY: hsa04914
Entry
hsa04914                    Pathway                                
Name
Progesterone-mediated oocyte maturation - Homo sapiens (human)
Description
Xenopus oocytes are naturally arrested at G2 of meiosis I. Exposure to either insulin/IGF-1 or the steroid hormone progesterone breaks this arrest and induces resumption of the two meiotic division cycles and maturation of the oocyte into a mature, fertilizable egg. This process is termed oocyte maturation. The transition is accompanied by an increase in maturation promoting factor (MPF or Cdc2/cyclin B) which precedes germinal vesicle breakdown (GVBD). Most reports point towards the Mos-MEK1-ERK2 pathway [where ERK is an extracellular signal-related protein kinase, MEK is a MAPK/ERK kinase and Mos is a p42(MAPK) activator] and the polo-like kinase/CDC25 pathway as responsible for the activation of MPF in meiosis, most likely triggered by a decrease in cAMP.
Class
Organismal Systems; Endocrine system
Pathway map
hsa04914  Progesterone-mediated oocyte maturation
hsa04914

Drug
D00066  Progesterone (JP18/USP/INN)
D00182  Norethindrone (USP)
D00289  Danazol (JP18/USP/INN)
D00585  Mifepristone (JAN/USAN/INN)
D00949  Hydroxyprogesterone caproate (JAN/USP/INN)
D00950  Levonorgestrel (JAN/USP/INN)
D00951  Medroxyprogesterone acetate (JP18/USP)
D00952  Megestrol acetate (USP)
D00953  Norethindrone acetate (USP)
D00954  Norgestrel (JP18/USP/INN)
D01159  Gestonorone caproate (JAN/USAN)
D01217  Dydrogesterone (JP18/USP/INN)
D01294  Ethynodiol diacetate (JAN/USP)
D01299  Chlormadinone acetate (JP18/USAN)
D01374  Allylestrenol (JAN/INN)
D01580  Lynestrenol (JAN/USAN)
D02367  Desogestrel (USAN/INN)
D02996  Asoprisnil (USAN/INN)
D03799  Dienogest (JAN/USAN/INN)
D03917  Drospirenone (JAN/USP/INN)
D04104  Etonogestrel (USAN/INN)
D04315  Gestaclone (USAN/INN)
D04316  Gestodene (USAN/INN)
D04885  Medrogestone (USAN/INN)
D05003  Methynodiol diacetate (USAN)
D05009  Metogest (USAN/INN)
D05205  Norelgestromin (USP/INN)
D05207  Norethynodrel (USAN)
D05209  Norgestimate (USP/INN)
D05308  Oxogestone phenpropionate (USAN)
D05679  Quingestanol acetate (USAN)
D05680  Quingestrone (USAN/INN)
D06003  Tanaproget (USAN/INN)
D06145  Tigestol (USAN/INN)
D06197  Tosagestin (USAN/INN)
D06235  Trimegestone (USAN/INN)
D07096  Aglepristone (INN)
D07220  Norgestrienone (INN)
D07222  Nomegestrol (USAN/INN)
D07223  Demegestone (INN)
D07670  Chlormadinone (INN)
D07939  Etynodiol (INN)
D07968  Flugestone (INN)
D08052  Hydroxyprogesterone (INN)
D08053  Hydroxyprogesterone 17alfa-acetate
D08166  Medroxyprogesterone (INN)
D08167  Megestrol (INN)
D08281  Nomegestrol acetate (USAN)
D08285  Norethisterone enantate
D08431  Promegestone (INN)
D09567  Ulipristal (USAN/INN)
D09571  Onapristone (INN)
D09687  Ulipristal acetate (JAN/USAN)
D09972  Telapristone acetate (USAN)
D10986  Segesterone acetate (USAN)
D10987  Segesterone (USAN/INN)
D11181  Vilaprisan (JAN/USAN/INN)
D12736  Lunresertib (USAN)
Other DBs
GO: 0001556
Organism
Homo sapiens (human) [GN:hsa]
Gene
5241  PGR; progesterone receptor [KO:K08556]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
2770  GNAI1; G protein subunit alpha i1 [KO:K04630]
2773  GNAI3; G protein subunit alpha i3 [KO:K04630]
2771  GNAI2; G protein subunit alpha i2 [KO:K04630]
107  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
108  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
109  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
115  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
6790  AURKA; aurora kinase A [KO:K11481] [EC:2.7.11.1]
64506  CPEB1; cytoplasmic polyadenylation element binding protein 1 [KO:K02602]
132864  CPEB2; cytoplasmic polyadenylation element binding protein 2 [KO:K02602]
22849  CPEB3; cytoplasmic polyadenylation element binding protein 3 [KO:K02602]
80315  CPEB4; cytoplasmic polyadenylation element binding protein 4 [KO:K02602]
245711  SPDYA; speedy/RINGO cell cycle regulator family member A [KO:K08694]
387778  SPDYC; speedy/RINGO cell cycle regulator family member C [KO:K08694]
100310812  SPDYE2B; speedy/RINGO cell cycle regulator family member E2B [KO:K08694]
100505767  SPDYE18; speedy/RINGO cell cycle regulator family member E18 [KO:K08694]
100996746  SPDYE11; speedy/RINGO cell cycle regulator family member E11 [KO:K08694]
102723555  SPDYE16; speedy/RINGO cell cycle regulator family member E16 [KO:K08694]
102723849  SPDYE17; speedy/RINGO cell cycle regulator family member E17 [KO:K08694]
285955  SPDYE1; speedy/RINGO cell cycle regulator family member E1 [KO:K08694]
388333  SPDYE4; speedy/RINGO cell cycle regulator family member E4 [KO:K08694]
441272  SPDYE3; speedy/RINGO cell cycle regulator family member E3 [KO:K08694]
441273  SPDYE2; speedy/RINGO cell cycle regulator family member E2 [KO:K08694]
442590  SPDYE5; speedy/RINGO cell cycle regulator family member E5 [KO:K08694]
729597  SPDYE6; speedy/RINGO cell cycle regulator family member E6 [KO:K08694]
105180391  SPDYE15; speedy/RINGO cell cycle regulator family member E15 [KO:K08694]
100101268  SPDYE12; speedy/RINGO cell cycle regulator family member E12 [KO:K08694]
124906603  putative speedy protein E9 [KO:K08694]
643862  SPDYE10; speedy/RINGO cell cycle regulator family member E10 [KO:K08694]
643909  SPDYE9; speedy/RINGO cell cycle regulator family member E9 [KO:K08694]
728524  SPDYE8; speedy/RINGO cell cycle regulator family member E8 [KO:K08694]
105180390  SPDYE13; speedy/RINGO cell cycle regulator family member E13 [KO:K08694]
641776  SPDYE14; speedy/RINGO cell cycle regulator family member E14 [KO:K08694]
1017  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
983  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
890  CCNA2; cyclin A2 [KO:K06627]
8900  CCNA1; cyclin A1 [KO:K06627]
4342  MOS; MOS proto-oncogene, serine/threonine kinase [KO:K04367] [EC:2.7.11.1]
3320  HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079]
3326  HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6197  RPS6KA3; ribosomal protein S6 kinase A3 [KO:K04373] [EC:2.7.11.1]
6195  RPS6KA1; ribosomal protein S6 kinase A1 [KO:K04373] [EC:2.7.11.1]
6196  RPS6KA2; ribosomal protein S6 kinase A2 [KO:K04373] [EC:2.7.11.1]
27330  RPS6KA6; ribosomal protein S6 kinase A6 [KO:K04373] [EC:2.7.11.1]
9088  PKMYT1; protein kinase, membrane associated tyrosine/threonine 1 [KO:K06633] [EC:2.7.11.1]
891  CCNB1; cyclin B1 [KO:K05868]
9133  CCNB2; cyclin B2 [KO:K21770]
85417  CCNB3; cyclin B3 [KO:K21771]
6793  STK10; serine/threonine kinase 10 [KO:K08837] [EC:2.7.11.1]
5347  PLK1; polo like kinase 1 [KO:K06631] [EC:2.7.11.21]
993  CDC25A; cell division cycle 25A [KO:K06645] [EC:3.1.3.48]
994  CDC25B; cell division cycle 25B [KO:K05866] [EC:3.1.3.48]
995  CDC25C; cell division cycle 25C [KO:K05867] [EC:3.1.3.48]
3630  INS; insulin [KO:K04526]
3479  IGF1; insulin like growth factor 1 [KO:K05459]
3480  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
5140  PDE3B; phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
369  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
699  BUB1; BUB1 mitotic checkpoint serine/threonine kinase [KO:K02178] [EC:2.7.11.1]
8379  MAD1L1; mitotic arrest deficient 1 like 1 [KO:K06679]
4085  MAD2L1; mitotic arrest deficient 2 like 1 [KO:K02537]
10459  MAD2L2; mitotic arrest deficient 2 like 2 [KO:K13728]
51343  FZR1; fizzy and cell division cycle 20 related 1 [KO:K03364]
64682  ANAPC1; anaphase promoting complex subunit 1 [KO:K03348]
29882  ANAPC2; anaphase promoting complex subunit 2 [KO:K03349]
996  CDC27; cell division cycle 27 [KO:K03350]
29945  ANAPC4; anaphase promoting complex subunit 4 [KO:K03351]
51433  ANAPC5; anaphase promoting complex subunit 5 [KO:K03352]
8881  CDC16; cell division cycle 16 [KO:K03353]
51434  ANAPC7; anaphase promoting complex subunit 7 [KO:K03354]
8697  CDC23; cell division cycle 23 [KO:K03355]
10393  ANAPC10; anaphase promoting complex subunit 10 [KO:K03357]
51529  ANAPC11; anaphase promoting complex subunit 11 [KO:K03358]
246184  CDC26; cell division cycle 26 [KO:K03359]
25847  ANAPC13; anaphase promoting complex subunit 13 [KO:K12456]
25906  ANAPC15; anaphase promoting complex subunit 15 [KO:K25228]
119504  ANAPC16; anaphase promoting complex subunit 16 [KO:K25229]
3835  KIF22; kinesin family member 22 [KO:K10403]
Compound
C00410  Progesterone
C00575  3',5'-Cyclic AMP
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C11554  1-Phosphatidyl-1D-myo-inositol 3,4-bisphosphate
Reference
PMID:12045215
  Authors
Schmitt A, Nebreda AR.
  Title
Signalling pathways in oocyte meiotic maturation.
  Journal
J Cell Sci 115:2457-9 (2002)
Reference
PMID:12084906
  Authors
Cato AC, Nestl A, Mink S.
  Title
Rapid actions of steroid receptors in cellular signaling pathways.
  Journal
Sci STKE 2002:RE9 (2002)
DOI:10.1126/stke.2002.138.re9
Reference
PMID:11730319
  Authors
Maller JL, Schwab MS, Roberts BT, Gross SD, Taieb FE, Tunquist BJ.
  Title
The pathway of MAP kinase mediation of CSF arrest in Xenopus oocytes.
  Journal
Biol Cell 93:27-33 (2001)
DOI:10.1016/S0248-4900(01)01127-3
Reference
PMID:11063930
  Authors
Nebreda AR, Ferby I.
  Title
Regulation of the meiotic cell cycle in oocytes.
  Journal
Curr Opin Cell Biol 12:666-75 (2000)
DOI:10.1016/S0955-0674(00)00150-2
Reference
PMID:10497333
  Authors
Ferrell JE Jr.
  Title
Xenopus oocyte maturation: new lessons from a good egg.
  Journal
Bioessays 21:833-42 (1999)
DOI:10.1002/(SICI)1521-1878(199910)21:10<833::AID-BIES5>3.0.CO;2-P
Reference
PMID:12374568
  Authors
Andersen CB, Sakaue H, Nedachi T, Kovacina KS, Clayberger C, Conti M, Roth RA.
  Title
Protein kinase B/Akt is essential for the insulin- but not progesterone-stimulated resumption of meiosis in Xenopus oocytes.
  Journal
Biochem J 369:227-38 (2003)
DOI:10.1042/BJ20021243
Reference
PMID:12477927
  Authors
Duckworth BC, Weaver JS, Ruderman JV.
  Title
G2 arrest in Xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A.
  Journal
Proc Natl Acad Sci U S A 99:16794-9 (2002)
DOI:10.1073/pnas.222661299
Reference
PMID:11148128
  Authors
Abrieu A, Doree M, Fisher D.
  Title
The interplay between cyclin-B-Cdc2 kinase (MPF) and MAP kinase during maturation of oocytes.
  Journal
J Cell Sci 114:257-67 (2001)
Related
pathway
hsa04010  MAPK signaling pathway
hsa04110  Cell cycle
KO pathway
ko04914   
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