KEGG   PATHWAY: pswi04912
Entry
pswi04912                   Pathway                                
Name
GnRH signaling pathway - Pseudoliparis swirei (Mariana hadal snailfish)
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
pswi04912  GnRH signaling pathway
pswi04912

Organism
Pseudoliparis swirei (Mariana hadal snailfish) [GN:pswi]
Gene
130207179  gnrh3; gonadotropin-releasing hormone 3 [KO:K05252]
130208471  gnrh2; progonadoliberin-2 [KO:K05252]
130197161  gonadotropin-releasing hormone II receptor-like [KO:K04280]
130192542  putative gonadotropin-releasing hormone II receptor [KO:K04280]
130194991  gnrhr4; gonadotropin releasing hormone receptor 4 [KO:K04280]
130213172  gonadotropin-releasing hormone II receptor-like [KO:K04280]
130207774  guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
130199258  gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
130193885  adcy1a; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
130197934  adenylate cyclase type 1-like isoform X1 [KO:K08041] [EC:4.6.1.1]
130194309  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
130212629  adcy2a; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
130206457  adcy3a; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
130202530  adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
130207209  adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
130200154  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
130199141  adenylate cyclase type 6-like isoform X1 [KO:K08046] [EC:4.6.1.1]
130192880  adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
130190901  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
130188722  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
130189473  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
130190218  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
130193455  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
130188307  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a isoform X1 [KO:K04345] [EC:2.7.11.11]
130198180  prkacbb; LOW QUALITY PROTEIN: protein kinase, cAMP-dependent, catalytic, beta b [KO:K04345] [EC:2.7.11.11]
130188618  atf4b; LOW QUALITY PROTEIN: activating transcription factor 4b [KO:K04374]
130190034  atf4a; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
130196152  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
130204941  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
130212230  guanine nucleotide-binding protein G(q) subunit alpha-like isoform X1 [KO:K04634]
130201190  gna11b; guanine nucleotide-binding protein subunit alpha-11b [KO:K04635]
130207272  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
130201430  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
130202601  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4-like isoform X1 [KO:K05858] [EC:3.1.4.11]
130202605  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
130211644  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
130208063  itpr1b; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
130208604  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
130194653  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
130199889  itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
130192292  calml4a; calmodulin-like protein 4a [KO:K02183]
130206962  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
130201284  calm1a; calmodulin-1a [KO:K02183]
130203085  calmodulin-1 [KO:K02183]
130210556  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
130190133  camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
130197335  camk2b1; calcium/calmodulin-dependent protein kinase (CaM kinase) II beta 1 isoform X1 [KO:K04515] [EC:2.7.11.17]
130206769  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
130203157  calcium/calmodulin-dependent protein kinase type II subunit gamma-like isoform X1 [KO:K04515] [EC:2.7.11.17]
130210158  calcium/calmodulin-dependent protein kinase type II subunit alpha-like [KO:K04515] [EC:2.7.11.17]
130205156  calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
130211907  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
130188951  prkcab; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
130189644  protein kinase C alpha type-like [KO:K02677] [EC:2.7.11.13]
130190241  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
130188608  protein kinase C beta type-like isoform X1 [KO:K19662] [EC:2.7.11.13]
130208665  protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]
130208821  prkcda; protein kinase C, delta a [KO:K06068] [EC:2.7.11.13]
130200799  cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
130200179  cacna1db; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
130208331  cacna1da; calcium channel, voltage-dependent, L type, alpha 1D subunit, a [KO:K04851]
130198907  cacna1fb; LOW QUALITY PROTEIN: calcium channel, voltage-dependent, L type, alpha 1F subunit [KO:K04853]
130198943  cacna1fa; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04853]
130208009  dihydropyridine-sensitive L-type skeletal muscle calcium channel subunit alpha-1-like isoform X1 [KO:K04857]
130199202  dihydropyridine-sensitive L-type skeletal muscle calcium channel subunit alpha-1-like [KO:K04857]
130204412  map3k2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
130188944  map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
130205998  map3k22; mitogen-activated protein kinase kinase kinase 22 [KO:K04421] [EC:2.7.11.25]
130206842  map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
130188772  dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:2.7.12.2]
130203445  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
130195729  mapk12a; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
130200204  mapk14a; mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
130200241  mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
130200493  mapk12b; mitogen-activated protein kinase 12b isoform X1 [KO:K04441] [EC:2.7.11.24]
130208586  mapk14b; mitogen-activated protein kinase 14B [KO:K04441] [EC:2.7.11.24]
130199473  mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
130199820  zgc:171775; STKc_p38 domain-containing protein [KO:K04441] [EC:2.7.11.24]
130203796  mapk7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
130194399  cytosolic phospholipase A2-like [KO:K16342] [EC:3.1.1.4]
130188979  cytosolic phospholipase A2 gamma-like isoform X1 [KO:K16342] [EC:3.1.1.4]
130207552  pla2g4f.1; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
130207553  cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
130207554  cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
130191964  pld2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
130206061  pld1b; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
130201035  pld1a; phospholipase D1a isoform X1 [KO:K01115] [EC:3.1.4.4]
130208564  proto-oncogene tyrosine-protein kinase Src-like isoform X1 [KO:K05704] [EC:2.7.10.2]
130199605  src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
130213488  cdc42l; cell division cycle 42, like [KO:K04393]
130208099  cell division control protein 42 homolog isoform X1 [KO:K04393]
130199341  cell division control protein 42 homolog isoform X1 [KO:K04393]
130188386  map2k4a; dual specificity mitogen-activated protein kinase kinase 4a isoform X1 [KO:K04430] [EC:2.7.12.2]
130203213  map2k4b; dual specificity mitogen-activated protein kinase kinase 4b [KO:K04430] [EC:2.7.12.2]
130190042  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
130206778  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
130209426  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
130203361  mapk8b; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
130205358  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
130194485  jun; transcription factor AP-1 [KO:K04448]
130197944  transcription factor Jun-like [KO:K04448]
130207029  lhb; lutropin subunit beta [KO:K08521]
130201476  cga; glycoprotein hormones alpha chain [KO:K08522]
130202125  ptk2bb; protein tyrosine kinase 2 beta, b isoform X1 [KO:K05871] [EC:2.7.10.2]
130204622  protein-tyrosine kinase 2-beta-like [KO:K05871] [EC:2.7.10.2]
130193110  mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
130197928  mmp14b; matrix metalloproteinase-14b [KO:K07763] [EC:3.4.24.80]
130211969  mmp14a; matrix metalloproteinase-14a [KO:K07763] [EC:3.4.24.80]
130209990  hbegfa; heparin-binding EGF-like growth factor a isoform X1 [KO:K08523]
130206605  melanoma receptor tyrosine-protein kinase-like [KO:K04361] [EC:2.7.10.1]
130188804  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
130189891  grb2a; growth factor receptor-bound protein 2a [KO:K04364]
130200969  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
130195891  GTPase HRas [KO:K02833]
130189051  zgc:55558; GTPase KRas [KO:K07827]
130195239  kras; GTPase KRas isoform X1 [KO:K07827]
130199044  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
130194985  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
130194253  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
130196458  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
130189362  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
130199025  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
130191840  LOW QUALITY PROTEIN: early growth response protein 1-like [KO:K09203]
130209192  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
pswi04010  MAPK signaling pathway
pswi04020  Calcium signaling pathway
pswi04060  Cytokine-cytokine receptor interaction
pswi04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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