KEGG   PATHWAY: pss04912
Entry
pss04912                    Pathway                                
Name
GnRH signaling pathway - Pelodiscus sinensis (Chinese soft-shelled turtle)
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
pss04912  GnRH signaling pathway
pss04912

Organism
Pelodiscus sinensis (Chinese soft-shelled turtle) [GN:pss]
Gene
106731384  GNRH1; progonadoliberin-1 [KO:K05252]
102447193  gonadotropin-releasing hormone II receptor-like isoform X2 [KO:K04280]
102454259  gonadotropin-releasing hormone II receptor-like isoform X2 [KO:K04280]
102447036  guanine nucleotide-binding protein G(s) subunit alpha isoform X2 [KO:K04632]
102445759  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102444057  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102463305  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
102451515  adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
102461993  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102448834  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
102449192  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
102448969  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
102448197  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
102454969  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102458631  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102449551  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102454459  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102455465  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
102455767  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102460883  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102449462  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102461092  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102462538  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
102453428  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102449833  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102459065  CALML3; calmodulin-like protein 3 [KO:K02183]
102462006  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
102462265  CALM1; calmodulin-1 [KO:K02183]
102454393  calmodulin-like [KO:K02183]
102452499  calmodulin isoform X2 [KO:K02183]
102458420  neo-calmodulin-like [KO:K02183]
102456219  calmodulin-A-like isoform X1 [KO:K02183]
102456795  CALM2; calmodulin-2 isoform X1 [KO:K02183]
102452008  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102445881  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X8 [KO:K04515] [EC:2.7.11.17]
102452528  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
102461772  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102459336  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102449325  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102451674  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
102451554  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
102447276  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
102453880  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S-like [KO:K04857]
102463619  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
102448094  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
102454880  mitogen-activated protein kinase kinase kinase 3-like isoform X1 [KO:K04421] [EC:2.7.11.25]
102454634  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X3 [KO:K04421] [EC:2.7.11.25]
102446659  MAP3K4; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
102454019  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
102461243  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102455939  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102462429  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102462672  MAPK12; mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
102448785  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102463278  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
102458559  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
102451624  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
102451529  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
106732453  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
106732455  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
102450053  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
102448586  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
102448831  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
102449068  cytosolic phospholipase A2 zeta-like isoform X2 [KO:K16342] [EC:3.1.1.4]
102449310  cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
102452248  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
102452501  cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102462875  cytosolic phospholipase A2 gamma-like isoform X1 [KO:K16342] [EC:3.1.1.4]
102446945  cytosolic phospholipase A2 gamma-like isoform X1 [KO:K16342] [EC:3.1.1.4]
112547289  uncharacterized protein LOC112547289 [KO:K16342] [EC:3.1.1.4]
112547387  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
102444412  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
102453375  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
102453139  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102462669  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102447391  CDC42; cell division control protein 42 homolog isoform X2 [KO:K04393]
102452927  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X4 [KO:K04430] [EC:2.7.12.2]
102463924  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102460734  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102459702  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102453224  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102455008  JUN; transcription factor AP-1 [KO:K04448]
102457567  CGA; glycoprotein hormones alpha chain [KO:K08522]
102454454  FSHB; follitropin subunit beta [KO:K05250]
102461932  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
102463152  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
102455005  HBEGF; proheparin-binding EGF-like growth factor isoform X2 [KO:K08523]
102443405  EGFR; epidermal growth factor receptor isoform X3 [KO:K04361] [EC:2.7.10.1]
102463609  GRB2; growth factor receptor-bound protein 2 isoform X2 [KO:K04364]
102453319  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102458741  SOS2; son of sevenless homolog 2 [KO:K03099]
102457627  HRAS; GTPase HRas isoform X2 [KO:K02833]
102447251  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
102450646  KRAS; GTPase KRas isoform X1 [KO:K07827]
102447991  NRAS; GTPase NRas [KO:K07828]
102458748  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102443595  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102457075  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102453948  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
102461012  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
pss04010  MAPK signaling pathway
pss04020  Calcium signaling pathway
pss04060  Cytokine-cytokine receptor interaction
pss04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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