KEGG   PATHWAY: ccay04912
Entry
ccay04912                   Pathway                                
Name
GnRH signaling pathway - Caretta caretta (Loggerhead 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
ccay04912  GnRH signaling pathway
ccay04912

Organism
Caretta caretta (Loggerhead turtle) [GN:ccay]
Gene
125626325  GNRH1; progonadoliberin-1 [KO:K05252]
125635119  progonadoliberin-2 [KO:K05252]
125626021  gonadotropin-releasing hormone II receptor-like [KO:K04280]
125643983  gonadotropin-releasing hormone II receptor-like [KO:K04280]
125644214  gonadotropin-releasing hormone II receptor-like [KO:K04280]
125622095  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
125631858  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
125631991  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
125634736  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
125622342  ADCY4; LOW QUALITY PROTEIN: adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
125644703  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
125627429  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
125645349  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
125632845  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
125643636  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
125641242  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
125627801  LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
125627827  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
125627830  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
125627831  cAMP-dependent protein kinase catalytic subunit alpha-like isoform X1 [KO:K04345] [EC:2.7.11.11]
125629188  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
125633375  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
125633377  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
125640618  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
125638409  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
125639566  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
125624778  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
125625000  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
125633502  CALM2; calmodulin-2 [KO:K02183]
125640639  calmodulin-A isoform X1 [KO:K02183]
125628181  CALM3; calmodulin-3 [KO:K02183]
125643358  CALML4; calmodulin-like protein 4 [KO:K02183]
125624266  CALML6; calmodulin-like protein 6 [KO:K02183]
125637734  CALM1; calmodulin-1 [KO:K02183]
125626428  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
125640510  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
125641039  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
125635283  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
125621080  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
125643497  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
125639345  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
125625969  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
125639955  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
125628302  voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
125625164  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
125636790  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
125644755  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
125626662  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
125631186  mitogen-activated protein kinase kinase kinase 3-like isoform X1 [KO:K04421] [EC:2.7.11.25]
125633990  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
125643689  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
125621197  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
125630653  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
125630656  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
125625009  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125625183  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
125639095  MAPK7; LOW QUALITY PROTEIN: mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
125641530  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
125622500  LOW QUALITY PROTEIN: cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
125622603  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
125629477  LOW QUALITY PROTEIN: cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
125638443  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
125638717  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
125638718  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
125638719  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
125638793  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
125638794  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
125638809  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
125639120  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
125628737  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
125642508  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
125621973  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
125624339  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
125620985  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
125627826  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
125640528  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125640964  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
125635834  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
125641435  JUN; transcription factor Jun [KO:K04448]
125634399  CGA; glycoprotein hormones alpha chain [KO:K08522]
125638816  FSHB; follitropin subunit beta [KO:K05250]
125634745  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
125620722  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
125622589  MMP14; LOW QUALITY PROTEIN: matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
125641628  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
125631817  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
125621222  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
125633300  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
125637809  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
125637699  HRAS; GTPase HRas [KO:K02833]
125628281  GTPase HRas-like [KO:K07827]
125624971  KRAS; GTPase KRas isoform X1 [KO:K07827]
125625144  NRAS; GTPase NRas [KO:K07828]
125640538  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125644013  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
125627064  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125623233  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
125638210  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125628416  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
125641463  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
ccay04010  MAPK signaling pathway
ccay04020  Calcium signaling pathway
ccay04060  Cytokine-cytokine receptor interaction
ccay04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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