KEGG   PATHWAY: mpah04912
Entry
mpah04912                   Pathway                                
Name
GnRH signaling pathway - Mus pahari (shrew mouse)
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
mpah04912  GnRH signaling pathway
mpah04912

Organism
Mus pahari (shrew mouse) [GN:mpah]
Gene
110325953  Gnrh1; progonadoliberin-1 isoform X1 [KO:K05252]
110330873  Gnrhr; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
110317699  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
110317700  neuroendocrine secretory protein 55 [KO:K04632]
110330584  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
110328764  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
110324646  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
110325439  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
110329393  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
110334500  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
110337453  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
110334612  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
110329624  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
110337220  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
110320995  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
110334651  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110336980  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
110326239  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
110336671  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
110317815  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
110318415  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110319646  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
110317210  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
110317251  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110338229  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110328293  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
110334170  Calml3; calmodulin-like protein 3 [KO:K02183]
110334182  calmodulin-4 [KO:K02183]
110336102  Calm2; calmodulin isoform X1 [KO:K02183]
110324261  Calm1; calmodulin [KO:K02183]
110336466  Calm3; calmodulin [KO:K02183]
110331006  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
110320932  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
110332832  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
110325574  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
110332714  Prkca; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
110320075  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110326026  Prkcd; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
110317086  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
110325961  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
110313596  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
110322010  Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
110328949  Map3k1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
110333106  Map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
110331495  Map3k3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
110338018  Map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
110331197  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
110331335  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
110334495  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110337896  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110337946  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110334829  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
110331679  Mapk7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
110317835  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
110319432  Pla2g4e; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
110318953  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
110336949  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
110318542  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
110321382  Pla2g4a; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
110331978  Pld2; LOW QUALITY PROTEIN: phospholipase D2 [KO:K01115] [EC:3.1.4.4]
110320262  Pld1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
110317793  Src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
110322847  Cdc42; cell division control protein 42 homolog isoform X1 [KO:K04393]
110331563  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
110336400  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
110330449  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110332652  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110325466  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110323252  Jun; transcription factor AP-1 [KO:K04448]
110332471  lutropin subunit beta [KO:K08521]
110338938  Cga; glycoprotein hormones alpha chain [KO:K08522]
110319484  Fshb; follitropin subunit beta [KO:K05250]
110325924  Ptk2b; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
110337240  Mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
110325048  Mmp14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
110333307  Hbegf; proheparin-binding EGF-like growth factor [KO:K08523]
110330480  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
110331195  Grb2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
110335780  Sos1; son of sevenless homolog 1 [KO:K03099]
110324314  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110318967  GTPase HRas-like isoform X1 [KO:K02833]
110319567  Hras; GTPase HRas [KO:K02833]
110338480  GTPase HRas-like [KO:K02833]
110333346  GTPase HRas-like [KO:K02833]
110316221  Kras; GTPase KRas isoform X1 [KO:K07827]
110320340  Nras; GTPase NRas [KO:K07828]
110314893  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110327244  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110326321  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110329343  Mapk1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110320020  Mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
110314286  Elk1; ETS domain-containing protein Elk-1 [KO:K04375]
110333149  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
mpah04010  MAPK signaling pathway
mpah04020  Calcium signaling pathway
mpah04024  cAMP signaling pathway
mpah04060  Cytokine-cytokine receptor interaction
mpah04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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