KEGG   PATHWAY: shab04912
Entry
shab04912                   Pathway                                
Name
GnRH signaling pathway - Strigops habroptila (Kakapo)
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
shab04912  GnRH signaling pathway
shab04912

Organism
Strigops habroptila (Kakapo) [GN:shab]
Gene
115618395  GNRH1; progonadoliberin-1 [KO:K05252]
115612790  gonadotropin-releasing hormone II receptor-like [KO:K04280]
115612950  putative gonadotropin-releasing hormone II receptor [KO:K04280]
115615081  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
115612821  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
115614173  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
115610050  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
115608320  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
115618663  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
115601291  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
115616417  ADCY8; LOW QUALITY PROTEIN: adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
115607555  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
115612311  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
115603010  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
115605443  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
115619152  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
115619403  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
115618049  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
115606933  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
115609999  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
115610001  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
115614357  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
115604669  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
115602289  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
115605423  calmodulin, striated muscle [KO:K02183]
115612722  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
115607428  CALM1; calmodulin-1 [KO:K02183]
115613433  CALM2; LOW QUALITY PROTEIN: calmodulin-2 [KO:K02183]
115605492  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
115618510  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
115609132  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
115615443  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
115616723  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
115606584  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
115614174  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
115605742  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
115614870  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
115602452  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
115619838  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
115607962  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
115617902  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
115609418  mitogen-activated protein kinase kinase kinase 3-like isoform X1 [KO:K04421] [EC:2.7.11.25]
115613582  MAP3K4; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
115607143  dual specificity mitogen-activated protein kinase kinase 3-like isoform X1 [KO:K04432] [EC:2.7.12.2]
115616735  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
115604848  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
115604850  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
115602374  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
115602375  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
115611589  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
115606022  cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
115606023  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
115617643  PLA2G4C; cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
115606494  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
115607297  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
115607298  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
115607299  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
115607300  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
115607301  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
115607302  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
115611611  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
115615139  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
115617517  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
115616509  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
115603011  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
115610508  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
115608097  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
115615620  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
115611576  JUN; transcription factor AP-1 [KO:K04448]
115609626  CGA; glycoprotein hormones alpha chain isoform X1 [KO:K08522]
115606906  FSHB; follitropin subunit beta [KO:K05250]
115609824  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
115600940  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
115619032  LOW QUALITY PROTEIN: 72 kDa type IV collagenase-like [KO:K01398] [EC:3.4.24.24]
115615555  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
115604109  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
115616466  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
115606686  SOS2; son of sevenless homolog 2 [KO:K03099]
115609915  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
115607639  HRAS; GTPase HRas [KO:K02833]
115602282  NRAS; GTPase NRas [KO:K07828]
115614046  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
115612648  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
115618167  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
115614282  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
115615966  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
shab04010  MAPK signaling pathway
shab04020  Calcium signaling pathway
shab04060  Cytokine-cytokine receptor interaction
shab04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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