KEGG   PATHWAY: elk04912
Entry
elk04912                    Pathway                                
Name
GnRH signaling pathway - Enhydra lutris kenyoni (northern sea 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
elk04912  GnRH signaling pathway
elk04912

Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111152669  progonadoliberin-1 [KO:K05252]
111141890  progonadoliberin-2 [KO:K05252]
111162044  LOW QUALITY PROTEIN: gonadotropin-releasing hormone II receptor-like [KO:K04280]
111149281  gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
111141614  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
111141312  neuroendocrine secretory protein 55 [KO:K04632]
111157054  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
111153427  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
111154044  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
111162403  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
111155044  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111157825  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
111157326  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
111146667  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
111156133  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
111162516  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
111143399  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111157635  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
111153498  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
111161857  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
111141432  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
111162302  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
111141620  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
111150005  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
111144005  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
111159979  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
111152507  inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
111158594  calmodulin-like [KO:K02183]
111158606  calmodulin-like protein 3 [KO:K02183]
111154855  calmodulin-like protein 6 [KO:K02183]
111160633  calmodulin-3 [KO:K02183]
111155835  calmodulin-2 [KO:K02183]
111148494  calmodulin-1 isoform X1 [KO:K02183]
111153268  calmodulin-like protein 4 isoform X1 [KO:K02183]
111140840  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
111145432  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
111153485  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
111156985  calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
111158087  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
111162208  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
111144045  protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
111159674  voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
111143738  voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
111150407  voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
111150995  voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
111156879  mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
111160868  mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
111158066  mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
111158665  mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
111139240  dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
111158041  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
111152267  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
111157625  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
111157628  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
111152183  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
111139244  mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
111150782  cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
111140157  LOW QUALITY PROTEIN: cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
111162039  cytosolic phospholipase A2 beta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
111140619  cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
111160468  cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
111161193  phospholipase D2 [KO:K01115] [EC:3.1.4.4]
111150121  phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
111141563  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
111154823  cell division control protein 42 homolog isoform X1 [KO:K04393]
111161210  dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
111161723  dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
111144860  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
111158897  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
111154016  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111143174  transcription factor AP-1 [KO:K04448]
111160757  lutropin subunit beta [KO:K08521]
111158799  glycoprotein hormones alpha chain [KO:K08522]
111150244  follitropin subunit beta [KO:K05250]
111153692  protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
111157340  72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
111158421  matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
111141144  proheparin-binding EGF-like growth factor [KO:K08523]
111157042  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111160411  growth factor receptor-bound protein 2 [KO:K04364]
111158354  son of sevenless homolog 1 isoform X1 [KO:K03099]
111160889  son of sevenless homolog 2 isoform X1 [KO:K03099]
111140316  GTPase HRas isoform X1 [KO:K02833]
111159984  GTPase KRas isoform X1 [KO:K07827]
111143238  GTPase NRas [KO:K07828]
111144322  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111153158  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111161815  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111162236  LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111142759  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111150586  ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
111140945  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
elk04010  MAPK signaling pathway
elk04020  Calcium signaling pathway
elk04024  cAMP signaling pathway
elk04060  Cytokine-cytokine receptor interaction
elk04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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