KEGG   PATHWAY: ggo04912
ggo04912                    Pathway                                

GnRH signaling pathway - Gorilla gorilla gorilla (western lowland gorilla)
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.
Organismal Systems; Endocrine system
Pathway map
ggo04912  GnRH signaling pathway

Gorilla gorilla gorilla (western lowland gorilla) [GN:ggo]
101126661  GNRH1; progonadoliberin-1 [KO:K05252]
101126857  GNRHR; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
101137503  LOW QUALITY PROTEIN: putative gonadotropin-releasing hormone II receptor [KO:K04280]
101132215  neuroendocrine secretory protein 55 [KO:K04632]
109023045  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X10 [KO:K04632]
101125943  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
101141389  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:]
101144031  ADCY3; adenylate cyclase type 3 isoform X4 [KO:K08043] [EC:]
101125890  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:]
101150181  ADCY5; adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:]
101139873  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:]
101126268  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:]
101142672  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
101145410  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:]
101151469  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:]
101134260  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
101139584  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101149651  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101129671  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
101149632  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
101140350  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:]
101153613  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:]
101129357  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:]
101154323  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:]
101151145  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101151502  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101124725  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X6 [KO:K04960]
101151475  CALML3; calmodulin-like protein 3 [KO:K02183]
101139013  CALM2; calmodulin-2 isoform X1 [KO:K02183]
101149474  CALM1; calmodulin-1 [KO:K02183]
101151113  CALML5; calmodulin-like protein 5 [KO:K02183]
101139397  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
101140627  calmodulin-2-like [KO:K02183]
101134676  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X29 [KO:K04515] [EC:]
101153594  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:]
101148194  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:]
101136547  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:]
101124828  PRKCA; protein kinase C alpha type [KO:K02677] [EC:]
101150691  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:]
101133370  PRKCD; protein kinase C delta type [KO:K06068] [EC:]
101134060  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
101140987  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
101131714  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
101150507  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
101136722  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:]
101149805  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:]
101148044  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X3 [KO:K04421] [EC:]
101152649  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:]
101145420  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:]
101142374  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:]
101134492  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:]
101134843  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
101148438  MAPK13; mitogen-activated protein kinase 13 isoform X3 [KO:K04441] [EC:]
101152640  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:]
101137450  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:]
109025233  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:]
101126764  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:]
101137812  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:]
101138793  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:]
101147399  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:]
101135150  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:]
101135996  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:]
101153251  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:]
101124029  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
101154090  dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:]
101143954  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:]
101124339  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X4 [KO:K04431] [EC:]
101152026  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:]
101124033  MAPK8; mitogen-activated protein kinase 8 isoform X2 [KO:K04440] [EC:]
101133141  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:]
101145729  JUN; transcription factor AP-1 [KO:K04448]
109024066  LHB; lutropin subunit beta precursor [KO:K08521]
101123865  CGA; glycoprotein hormones alpha chain [KO:K08522]
101143526  FSHB; follitropin subunit beta [KO:K05250]
101135800  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:]
101147102  MMP2; 72 kDa type IV collagenase isoform X1 [KO:K01398] [EC:]
101142469  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:]
101138938  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
101126190  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:]
101133976  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101130824  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101137539  SOS2; son of sevenless homolog 2 [KO:K03099]
101136425  HRAS; GTPase HRas isoform X1 [KO:K02833]
101144039  KRAS; GTPase KRas isoform X1 [KO:K07827]
101146562  NRAS; GTPase NRas [KO:K07828]
101136454  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X3 [KO:K04366] [EC:]
101132391  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:]
101126885  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
101140164  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
101135988  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:]
101133308  ELK1; LOW QUALITY PROTEIN: ETS domain-containing protein Elk-1 [KO:K04375]
101153225  EGR1; early growth response protein 1 [KO:K09203]
C00076  Calcium cation
C00165  Diacylglycerol
C00219  Arachidonate
C00416  Phosphatidate
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
Ruf F, Sealfon SC.
Genomics view of gonadotrope signaling circuits.
Trends Endocrinol Metab 15:331-8 (2004)
Harrison GS, Wierman ME, Nett TM, Glode LM.
Gonadotropin-releasing hormone and its receptor in normal and malignant cells.
Endocr Relat Cancer 11:725-48 (2004)
Pawson AJ, McNeilly AS.
The pituitary effects of GnRH.
Anim Reprod Sci 88:75-94 (2005)
DeGroot LJ, Jameson JL (ed).
Endocrinology (Fifth edition)
Elsevier Saunders (2006)
Naor Z, Benard O, Seger R.
Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor.
Trends Endocrinol Metab 11:91-9 (2000)
Ruf F, Fink MY, Sealfon SC.
Structure of the GnRH receptor-stimulated signaling network: insights from genomics.
Front Neuroendocrinol 24:181-99 (2003)
Farshori PQ, Shah BH, Arora KK, Martinez-Fuentes A, Catt KJ.
Activation and nuclear translocation of PKCdelta, Pyk2 and ERK1/2 by gonadotropin releasing hormone in HEK293 cells.
J Steroid Biochem Mol Biol 85:337-47 (2003)
Shah BH, Catt KJ.
Matrix metalloproteinases in reproductive endocrinology.
Trends Endocrinol Metab 15:47-9 (2004)
Roelle S, Grosse R, Aigner A, Krell HW, Czubayko F, Gudermann T.
Matrix metalloproteinases 2 and 9 mediate epidermal growth factor receptor transactivation by gonadotropin-releasing hormone.
J Biol Chem 278:47307-18 (2003)
Naor Z
Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor.
Front Neuroendocrinol 30:10-29 (2009)
ggo04010  MAPK signaling pathway
ggo04020  Calcium signaling pathway
ggo04024  cAMP signaling pathway
ggo04060  Cytokine-cytokine receptor interaction
ggo04080  Neuroactive ligand-receptor interaction
KO pathway

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