KEGG   PATHWAY: psex04912
Entry
psex04912                   Pathway                                
Name
GnRH signaling pathway - Polypterus senegalus (gray bichir)
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
psex04912  GnRH signaling pathway
psex04912

Organism
Polypterus senegalus (gray bichir) [GN:psex]
Gene
120539760  progonadoliberin-1-like [KO:K05252]
120532739  gnrh2; progonadoliberin-2 isoform X1 [KO:K05252]
120541565  gnrhr4; gonadotropin releasing hormone receptor 4 [KO:K04280]
120528595  gonadotropin-releasing hormone II receptor-like isoform X1 [KO:K04280]
120518685  gonadotropin-releasing hormone II receptor-like [KO:K04280]
120514201  gnas; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
120529518  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
120515751  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
120526110  adcy3a; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
120524043  adenylate cyclase type 2-like [KO:K08044] [EC:4.6.1.1]
120530718  adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
120524822  adcy6a; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
120535204  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
120529809  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
120543008  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
120514851  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
120541109  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
120527303  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
120537716  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
120518946  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
120539203  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
120516316  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
120516513  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
120540181  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
120534185  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
120526198  itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
120530526  calglandulin-like [KO:K02183]
120521606  calmodulin-like [KO:K02183]
120538670  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
120539370  calm3b; calmodulin 3b (phosphorylase kinase, delta) [KO:K02183]
120523494  calmodulin-alpha-like [KO:K02183]
120541657  calml4a; calmodulin-like protein 4a [KO:K02183]
120516414  calmodulin-alpha-like [KO:K02183]
120516454  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
120516564  calmodulin-like [KO:K02183]
120516565  calmodulin-like [KO:K02183]
120518519  calmodulin-1 [KO:K02183]
120538731  camk2g2; calcium/calmodulin-dependent protein kinase type II delta chain isoform X1 [KO:K04515] [EC:2.7.11.17]
120538827  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
120533088  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
120542230  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
120517149  protein kinase C alpha type-like [KO:K02677] [EC:2.7.11.13]
120542651  prkcba; protein kinase C, beta a isoform X1 [KO:K19662] [EC:2.7.11.13]
120540466  protein kinase C delta type-like isoform X1 [KO:K06068] [EC:2.7.11.13]
120540046  voltage-dependent L-type calcium channel subunit alpha-1C-like isoform X1 [KO:K04850]
120542743  voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04853]
120525930  voltage-dependent L-type calcium channel subunit alpha-1S-like isoform X1 [KO:K04857]
120532605  map3k1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
120531266  map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
120517514  map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
120529593  map3k22; mitogen-activated protein kinase kinase kinase 22 [KO:K04421] [EC:2.7.11.25]
120516902  map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
120543271  map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04432] [EC:2.7.12.2]
120539589  mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
120539590  mapk12a; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
120540369  zgc:171775; STKc_p38 domain-containing protein [KO:K04441] [EC:2.7.11.24]
120526229  mapk14b; mitogen-activated protein kinase 14B isoform X1 [KO:K04441] [EC:2.7.11.24]
120526230  mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
120519620  mapk7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
120514410  cytosolic phospholipase A2-like [KO:K16342] [EC:3.1.1.4]
120518783  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
120523462  si:ch211-168k14.2; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
120525155  pld2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
120534121  pld1a; phospholipase D1a isoform X1 [KO:K01115] [EC:3.1.4.4]
120514252  src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
120530955  cdc42; cell division control protein 42 homolog isoform X1 [KO:K04393]
120535673  cell division control protein 42 homolog [KO:K04393]
120517075  dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
120540006  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
120542011  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
120527417  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
120514504  jun; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
120533062  june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
120526828  cga; glycoprotein hormones alpha chain [KO:K08522]
120526386  ptk2ba; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
120535223  mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
120524476  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
120542822  proheparin-binding EGF-like growth factor [KO:K08523]
120529821  epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
120517145  grb2a; growth factor receptor-bound protein 2a [KO:K04364]
120516982  son of sevenless homolog 1-like isoform X1 [KO:K03099]
120518289  sos2; son of sevenless homolog 2 [KO:K03099]
120523258  GTPase HRas [KO:K02833]
120534191  GTPase KRas isoform X1 [KO:K07827]
120542190  GTPase HRas-like [KO:K07827]
120526283  nras; GTPase NRas [KO:K07828]
120540276  raf1b; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
120541670  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
120537759  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
120540631  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120536571  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120542848  elk1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
120542185  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
psex04010  MAPK signaling pathway
psex04020  Calcium signaling pathway
psex04060  Cytokine-cytokine receptor interaction
psex04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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