KEGG   PATHWAY: hsa04914Help
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
BRITE hierarchy
Pathway map
Progesterone-mediated oocyte maturation
hsa04914

All organismsOrtholog table
Module
APC/C complex [PATH:hsa04914]
Disease
H01274  
Growth delay due to insulin-like growth factor I resistance
Drug
D00066  
Progesterone (JP17/USP/INN)
D00182  
Norethisterone (JP17)
D00231  
Amrinone (JAN/INN)
D00289  
Danazol (JP17/USP/INN)
D00417  
Milrinone (JAN/USP/INN)
D00585  
Mifepristone (USAN/INN)
D00949  
Hydroxyprogesterone caproate (JAN/USP/INN)
D00950  
Levonorgestrel (JAN/USP/INN)
D00951  
Medroxyprogesterone acetate (JP17/USP)
D00952  
Megestrol acetate (USAN)
D00953  
Norethisterone acetate (JAN)
D00954  
Norgestrel (JP17/USP/INN)
D01133  
Pimobendan (JAN/USAN/INN)
D01159  
Gestonorone caproate (JAN/USAN)
D01198  
Toborinone (JAN/USAN/INN)
D01217  
Dydrogesterone (JP17/USP/INN)
D01294  
Ethynodiol diacetate (JAN/USP)
D01299  
Chlormadinone acetate (JP17/USAN)
D01374  
Allylestrenol (JAN/INN)
D01580  
Lynestrenol (JAN/USAN)
D01690  
Vesnarinone (JAN/USAN/INN)
D01896  
Cilostazol (JP17/USAN/INN)
D02084  
Inamrinone ethylenelactate
D02085  
Milrinone lactate
D02367  
Desogestrel (USAN/INN)
D02996  
Asoprisnil (USAN/INN)
D03297  
Mecasermin (genetical recombination) (JAN)
D03799  
Dienogest (JAN/USAN/INN)
D04004  
Enoximone (USAN/INN)
D04104  
Etonogestrel (USAN/INN)
D04316  
Gestodene (USAN/INN)
D04508  
Imazodan hydrochloride (USAN)
D04529  
Indolidan (USAN/INN)
D04628  
Isomazole hydrochloride (USAN)
D04720  
Levosimendan (USAN/INN)
D04751  
Lixazinone sulfate (USAN)
D04870  
Mecasermin rinfabate (USAN/INN)
D04885  
Medrogestone (USAN/INN)
D05003  
Methynodiol diacetate (USAN)
D05209  
Norgestimate (USP/INN)
D05679  
Quingestanol acetate (USAN)
D07220  
Norgestrienone (INN)
D07222  
Nomegestrol (USAN/INN)
D07223  
Demegestone (INN)
D07670  
Chlormadinone (INN)
D07939  
Etynodiol (INN)
D08052  
Hydroxyprogesterone (INN)
D08053  
Hydroxyprogesterone 17alfa-acetate
D08166  
Medroxyprogesterone (INN)
D08167  
Megestrol (INN)
D08281  
Nomegestrol acetate (USAN)
D08285  
Norethisterone enantate
D08431  
Promegestone (INN)
D09375  
Retaspimycin (USAN/INN)
D09376  
Retaspimycin hydrochloride (USAN)
D09571  
Onapristone (INN)
D09972  
Telapristone acetate (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
5241  
PGR; progesterone receptor [KO:K08556]
5295  
PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [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]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [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 (brain) [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 (brain) [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 (brain) [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]
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]
SPDYE2B; speedy/RINGO cell cycle regulator family member E2B [KO:K08694]
SPDYE18; speedy/RINGO cell cycle regulator family member E18 [KO:K08694]
SPDYE11; speedy/RINGO cell cycle regulator family member E11 [KO:K08694]
SPDYE16; speedy/RINGO cell cycle regulator family member E16 [KO:K08694]
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]
1017  
CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
983  
CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.23 2.7.11.22]
890  
CCNA2; cyclin A2 [KO:K06627]
8900  
CCNA1; cyclin A1 [KO:K06627]
4342  
MOS; v-mos Moloney murine sarcoma viral oncogene homolog [KO:K04367] [EC:2.7.11.1]
3320  
HSP90AA1; heat shock protein 90kDa alpha family class A member 1 [KO:K04079]
3326  
HSP90AB1; heat shock protein 90kDa 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:K05868]
85417  
CCNB3; cyclin B3 [KO:K05868]
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; MAD1 mitotic arrest deficient like 1 [KO:K06638]
4085  
MAD2L1; MAD2 mitotic arrest deficient-like 1 (yeast) [KO:K02537]
10459  
MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
51343  
FZR1; fizzy/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]
Compound
C00410  
Progesterone
C00575  
3',5'-Cyclic AMP
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
C11554  
1-Phosphatidyl-1D-myo-inositol 3,4-bisphosphate
Reference
  Authors
Schmitt A, Nebreda AR.
  Title
Signalling pathways in oocyte meiotic maturation.
  Journal
J Cell Sci 115:2457-9 (2002)
Reference
  Authors
Cato AC, Nestl A, Mink S.
  Title
Rapid actions of steroid receptors in cellular signaling pathways.
  Journal
Sci STKE 2002:RE9 (2002)
Reference
  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)
Reference
  Authors
Nebreda AR, Ferby I.
  Title
Regulation of the meiotic cell cycle in oocytes.
  Journal
Curr Opin Cell Biol 12:666-75 (2000)
Reference
  Authors
Ferrell JE Jr.
  Title
Xenopus oocyte maturation: new lessons from a good egg.
  Journal
Bioessays 21:833-42 (1999)
Reference
  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)
Reference
  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)
Reference
  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)
KO pathway
 

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