KEGG   PATHWAY: malb04912
Entry
malb04912                   Pathway                                
Name
GnRH signaling pathway - Monopterus albus (swamp eel)
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
malb04912  GnRH signaling pathway
malb04912

Organism
Monopterus albus (swamp eel) [GN:malb]
Gene
109956123  gnrh2; progonadoliberin-2 [KO:K05252]
109954912  gnrh1; progonadoliberin-1 isoform X1 [KO:K05252]
109961329  progonadoliberin-3 [KO:K05252]
109953723  gonadotropin-releasing hormone II receptor-like [KO:K04280]
109967090  gonadotropin-releasing hormone II receptor-like isoform X1 [KO:K04280]
109971570  gonadotropin-releasing hormone II receptor-like [KO:K04280]
109973646  gonadotropin-releasing hormone II receptor-like [KO:K04280]
109970856  gonadotropin-releasing hormone II receptor-like [KO:K04280]
109970238  guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
109970020  gnas; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
109961254  adenylate cyclase type 1-like isoform X1 [KO:K08041] [EC:4.6.1.1]
109957656  adenylate cyclase type 1-like isoform X1 [KO:K08041] [EC:4.6.1.1]
109958353  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
109971723  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
109952263  LOW QUALITY PROTEIN: adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
109974016  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
109966043  adcy6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
109968886  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
109955816  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109971087  LOW QUALITY PROTEIN: adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
109970259  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
109972278  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
109972902  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
109952408  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109957708  cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
109958253  cAMP-dependent protein kinase catalytic subunit beta-like isoform X1 [KO:K04345] [EC:2.7.11.11]
109965931  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109951619  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
109972433  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
109961546  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
109972348  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
109964012  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
109952059  guanine nucleotide-binding protein G(q) subunit alpha-like isoform X1 [KO:K04635]
109961174  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
109962200  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
109962203  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
109965817  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
109968365  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
109956043  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
109956224  LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1-like [KO:K04958]
109970756  itpr2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
109970976  itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
109963360  calml4; calmodulin-like protein 4 [KO:K02183]
109959045  calml6; calmodulin-like protein 6 isoform X1 [KO:K02183]
109974113  calm2; calmodulin [KO:K02183]
109973529  calm3; calmodulin [KO:K02183]
109972810  calmodulin [KO:K02183]
109969805  calmodulin-alpha-like [KO:K02183]
109961060  calcium/calmodulin-dependent protein kinase type II delta chain-like [KO:K04515] [EC:2.7.11.17]
109962949  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
109957186  calcium/calmodulin-dependent protein kinase type II delta 1 chain [KO:K04515] [EC:2.7.11.17]
109955133  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
109958384  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
109953086  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
109952362  calcium/calmodulin-dependent protein kinase type II subunit beta-like [KO:K04515] [EC:2.7.11.17]
109971535  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
109971994  protein kinase C alpha type-like [KO:K02677] [EC:2.7.11.13]
109958847  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109968203  protein kinase C beta type-like isoform X1 [KO:K19662] [EC:2.7.11.13]
109964491  protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]
109959866  voltage-dependent L-type calcium channel subunit alpha-1C-like isoform X1 [KO:K04850]
109951925  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04851]
109970859  cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
109953071  voltage-dependent L-type calcium channel subunit alpha-1F-like isoform X1 [KO:K04853]
109968827  cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
109955649  map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
109963171  map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
109961492  mitogen-activated protein kinase kinase kinase 3-like isoform X1 [KO:K04421] [EC:2.7.11.25]
109961895  map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
109962725  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
109972262  dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:2.7.12.2]
109961826  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
109956159  mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
109971135  mitogen-activated protein kinase 11-like isoform X1 [KO:K04441] [EC:2.7.11.24]
109969176  mitogen-activated protein kinase 14A-like isoform X1 [KO:K04441] [EC:2.7.11.24]
109967181  mitogen-activated protein kinase 14A-like [KO:K04441] [EC:2.7.11.24]
109967219  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
109963593  mitogen-activated protein kinase 7-like isoform X1 [KO:K04464] [EC:2.7.11.24]
109961725  pla2g4a; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
109973708  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
109959498  LOW QUALITY PROTEIN: phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
109951086  LOW QUALITY PROTEIN: phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
109969617  pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
109958168  proto-oncogene tyrosine-protein kinase Src-like isoform X1 [KO:K05704] [EC:2.7.10.2]
109970991  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
109971977  cell division control protein 42 homolog [KO:K04393]
109968874  cell division control protein 42 homolog [KO:K04393]
109966191  cell division control protein 42 homolog [KO:K04393]
109966735  cell division control protein 42 homolog isoform X1 [KO:K04393]
109962855  dual specificity mitogen-activated protein kinase kinase 4-like isoform X1 [KO:K04430] [EC:2.7.12.2]
109966673  dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:2.7.12.2]
109966260  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
109961054  mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109973158  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
109969172  mitogen-activated protein kinase 8-like [KO:K04440] [EC:2.7.11.24]
109972323  mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
109952420  LOW QUALITY PROTEIN: transcription factor AP-1-like [KO:K04448]
109970646  jun; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
109963826  gonadotropin subunit beta-2 [KO:K08521]
109955066  cga; glycoprotein hormones alpha chain [KO:K08522]
109960575  protein-tyrosine kinase 2-beta-like [KO:K05871] [EC:2.7.10.2]
109970009  LOW QUALITY PROTEIN: protein-tyrosine kinase 2-beta-like [KO:K05871] [EC:2.7.10.2]
109955873  mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
109962674  LOW QUALITY PROTEIN: matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
109974431  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
109954704  proheparin-binding EGF-like growth factor [KO:K08523]
109953264  melanoma receptor tyrosine-protein kinase-like [KO:K04361] [EC:2.7.10.1]
109955384  LOW QUALITY PROTEIN: epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
109973503  grb2; growth factor receptor-bound protein 2 [KO:K04364]
109973380  sos2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
109971796  sos1; son of sevenless homolog 1 [KO:K03099]
109970774  hras; GTPase HRas [KO:K02833]
109958833  GTPase HRas-like [KO:K07827]
109970760  kras; GTPase KRas isoform X1 [KO:K07827]
109966113  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109971216  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
109974179  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109967020  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
109958888  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
109951143  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109968600  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
109971184  egr1; early growth response protein 1 [KO:K09203]
109974215  early growth response protein 1-like [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
malb04010  MAPK signaling pathway
malb04020  Calcium signaling pathway
malb04060  Cytokine-cytokine receptor interaction
malb04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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