KEGG   PATHWAY: caty04912
Entry
caty04912                   Pathway                                
Name
GnRH signaling pathway - Cercocebus atys (sooty mangabey)
Description
Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnRHR is coupled to Gq/11 proteins to activate phospholipase C which transmits its signal to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG activates the intracellular protein kinase C (PKC) pathway and IP3 stimulates release of intracellular calcium. In addition to the classical Gq/11, coupling of Gs is occasionally observed in a cell-specific fashion. Signaling downstream of protein kinase C (PKC) leads to transactivation of the epidermal growth factor (EGF) receptor and activation of mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. Active MAPKs translocate to the nucleus, resulting in activation of transcription factors and rapid induction of early genes.
Class
Organismal Systems; Endocrine system
Pathway map
caty04912  GnRH signaling pathway
caty04912

Organism
Cercocebus atys (sooty mangabey) [GN:caty]
Gene
105579193  GNRH1; progonadoliberin-1 isoform X1 [KO:K05252]
105582156  GNRH2; progonadoliberin-2 isoform X1 [KO:K05252]
105592861  LOW QUALITY PROTEIN: gonadotropin-releasing hormone II receptor-like [KO:K04280]
105596089  GNRHR; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
105585318  neuroendocrine secretory protein 55 [KO:K04632]
105585319  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
105588320  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105585972  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
105578529  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
105600225  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
105589787  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
105580404  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105588901  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105588369  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
105572097  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
105593561  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105601580  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105584148  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
105572871  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105584209  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105591769  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
105577494  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
105574260  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105582089  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105582092  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105585726  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105601409  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
105593244  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105600970  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
105594435  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
105595186  CALM3; calmodulin isoform X1 [KO:K02183]
105596563  CALM1; calmodulin [KO:K02183]
105581752  calmodulin-like [KO:K02183]
105597438  CALML3; calmodulin-like protein 3 [KO:K02183]
105597439  CALML5; calmodulin-like protein 5 [KO:K02183]
105590605  CALM2; calmodulin [KO:K02183]
105571464  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
105596908  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
105589879  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
105597344  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
105599331  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105586076  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
105585581  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
105582968  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
105585586  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
105573107  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
105575216  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
105599635  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
105592087  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
105590736  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
105594238  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
105593750  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
105577799  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
105592690  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
105592727  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105586882  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
105586884  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
105593716  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
105579889  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
105595443  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
105574211  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
105574213  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
105574214  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
105574265  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
105586073  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
105583465  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
105582359  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
105595026  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
105571986  cell division control protein 42 homolog [KO:K04393]
105581389  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
105589128  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
105590417  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105591436  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105576775  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105595973  JUN; transcription factor AP-1 [KO:K04448]
105595269  LHB; lutropin subunit beta isoform X1 [KO:K08521]
105589009  CGA; glycoprotein hormones alpha chain [KO:K08522]
105586751  FSHB; follitropin subunit beta [KO:K05250]
105579176  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
105588567  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
105598793  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
105599879  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
105588269  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
105577731  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105586728  SOS2; son of sevenless homolog 2 [KO:K03099]
105597205  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105577198  HRAS; GTPase HRas isoform X1 [KO:K02833]
105585038  KRAS; GTPase KRas isoform X1 [KO:K07827]
105596344  NRAS; GTPase NRas isoform X1 [KO:K07828]
105585803  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105601165  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105591800  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
105598233  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105598850  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105590499  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
105599843  EGR1; early growth response protein 1 [KO:K09203]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00219  Arachidonate
C00416  Phosphatidate
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:15350605
  Authors
Ruf F, Sealfon SC.
  Title
Genomics view of gonadotrope signaling circuits.
  Journal
Trends Endocrinol Metab 15:331-8 (2004)
DOI:10.1016/j.tem.2004.07.008
Reference
PMID:15613448
  Authors
Harrison GS, Wierman ME, Nett TM, Glode LM.
  Title
Gonadotropin-releasing hormone and its receptor in normal and malignant cells.
  Journal
Endocr Relat Cancer 11:725-48 (2004)
DOI:10.1677/erc.1.00777
Reference
PMID:15982836
  Authors
Pawson AJ, McNeilly AS.
  Title
The pituitary effects of GnRH.
  Journal
Anim Reprod Sci 88:75-94 (2005)
DOI:10.1016/j.anireprosci.2005.05.010
Reference
  Authors
DeGroot LJ, Jameson JL (ed).
  Title
Endocrinology (Fifth edition)
  Journal
Elsevier Saunders (2006)
Reference
PMID:10707049
  Authors
Naor Z, Benard O, Seger R.
  Title
Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor.
  Journal
Trends Endocrinol Metab 11:91-9 (2000)
DOI:10.1016/S1043-2760(99)00232-5
Reference
PMID:14596811
  Authors
Ruf F, Fink MY, Sealfon SC.
  Title
Structure of the GnRH receptor-stimulated signaling network: insights from genomics.
  Journal
Front Neuroendocrinol 24:181-99 (2003)
DOI:10.1016/S0091-3022(03)00027-X
Reference
PMID:12943720
  Authors
Farshori PQ, Shah BH, Arora KK, Martinez-Fuentes A, Catt KJ.
  Title
Activation and nuclear translocation of PKCdelta, Pyk2 and ERK1/2 by gonadotropin releasing hormone in HEK293 cells.
  Journal
J Steroid Biochem Mol Biol 85:337-47 (2003)
DOI:10.1016/S0960-0760(03)00226-7
Reference
PMID:15080147
  Authors
Shah BH, Catt KJ.
  Title
Matrix metalloproteinases in reproductive endocrinology.
  Journal
Trends Endocrinol Metab 15:47-9 (2004)
DOI:10.1016/j.tem.2004.01.004
Reference
PMID:12963732
  Authors
Roelle S, Grosse R, Aigner A, Krell HW, Czubayko F, Gudermann T.
  Title
Matrix metalloproteinases 2 and 9 mediate epidermal growth factor receptor transactivation by gonadotropin-releasing hormone.
  Journal
J Biol Chem 278:47307-18 (2003)
DOI:10.1074/jbc.M304377200
Reference
PMID:18708085
  Authors
Naor Z
  Title
Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor.
  Journal
Front Neuroendocrinol 30:10-29 (2009)
DOI:10.1016/j.yfrne.2008.07.001
Related
pathway
caty04010  MAPK signaling pathway
caty04020  Calcium signaling pathway
caty04024  cAMP signaling pathway
caty04060  Cytokine-cytokine receptor interaction
caty04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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