KEGG   PATHWAY: llv04912
Entry
llv04912                    Pathway                                
Name
GnRH signaling pathway - Lutra lutra (Eurasian river otter)
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
llv04912  GnRH signaling pathway
llv04912

Organism
Lutra lutra (Eurasian river otter) [GN:llv]
Gene
125108513  progonadoliberin-2-like [KO:K05252]
125092896  progonadoliberin-1 isoform X1 [KO:K05252]
125093773  gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
125097114  LOW QUALITY PROTEIN: gonadotropin-releasing hormone II receptor-like [KO:K04280]
125108178  neuroendocrine secretory protein 55 [KO:K04632]
125108177  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
125081029  adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
125099871  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
125108687  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
125104720  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
125103305  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
125106490  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
125088705  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
125098951  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
125091072  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
125083608  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
125097539  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
125106338  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
125083151  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
125087086  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
125108695  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
125108926  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
125110237  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
125105190  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
125109360  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
125107116  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
125103123  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
125099896  calmodulin-1-like [KO:K02183]
125107709  calmodulin-like protein 3 [KO:K02183]
125092830  calmodulin-1 [KO:K02183]
125109105  calmodulin-1 [KO:K02183]
125104272  calmodulin-like protein 4 isoform X1 [KO:K02183]
125104293  calmodulin-1 [KO:K02183]
125097034  calmodulin-like protein 6 [KO:K02183]
125097532  calmodulin-1-like [KO:K02183]
125089454  calmodulin-1 [KO:K02183]
125100120  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
125084354  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
125093303  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
125080735  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
125087644  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
125090366  protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
125078754  protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
125107204  voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
125078710  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04851]
125091668  voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
125086002  voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
125101058  mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
125096067  mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
125087832  mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
125102269  mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
125087473  dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
125087142  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
125101777  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125103018  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
125096321  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
125106184  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
125106185  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
125088025  mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
125086218  cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
125104288  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
125104913  cytosolic phospholipase A2 delta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
125104914  cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
125105491  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
125100378  phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
125087157  phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
125108930  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
125107993  cell division control protein 42 homolog [KO:K04393]
125094750  cell division control protein 42 homolog [KO:K04393]
125097697  cell division control protein 42 homolog isoform X1 [KO:K04393]
125087109  LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:2.7.12.2]
125085818  dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
125099732  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
125084526  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125093137  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125098159  transcription factor Jun [KO:K04448]
125089666  lutropin subunit beta [KO:K08521]
125103297  glycoprotein hormones alpha chain [KO:K08522]
125080146  follitropin subunit beta [KO:K05250]
125092973  protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
125089554  72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
125104089  matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
125100868  proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
125080419  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
125087106  growth factor receptor-bound protein 2 [KO:K04364]
125109653  LOW QUALITY PROTEIN: son of sevenless homolog 1-like [KO:K03099]
125104149  son of sevenless homolog 2 isoform X1 [KO:K03099]
125078621  GTPase HRas isoform X1 [KO:K02833]
125106241  GTPase KRas isoform X1 [KO:K07827]
125098043  GTPase NRas [KO:K07828]
125108469  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125105594  dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
125086704  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125081690  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125090203  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125091401  ETS domain-containing protein Elk-1 [KO:K04375]
125100705  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
llv04010  MAPK signaling pathway
llv04020  Calcium signaling pathway
llv04024  cAMP signaling pathway
llv04060  Cytokine-cytokine receptor interaction
llv04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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