Entry Name GnRH signaling pathway - Canis lupus familiaris (dog)
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 systemBRITE hierarchy
Pathway map Organism Canis lupus familiaris (dog) [GN:
cfa ]
Gene 100856190 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
119863888 CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
403483 CGA; glycoprotein hormones alpha chain precursor [KO:K08522 ]
403516 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X17 [KO:K04850 ]
403718 GNRHR; gonadotropin-releasing hormone receptor [KO:K04280 ]
403914 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
403928 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
403943 GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632 ]
474503 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
476034 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858 ] [EC:3.1.4.11 ]
476548 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
477160 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
478351 CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183 ]
479975 PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345 ] [EC:2.7.11.11 ]
480454 MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433 ] [EC:2.7.12.2 ]
480915 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
481746 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960 ]
482687 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
483312 GRB2; growth factor receptor-bound protein 2 [KO:K04364 ]
484648 RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366 ] [EC:2.7.11.1 ]
484724 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X15 [KO:K04851 ]
485004 MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431 ] [EC:2.7.12.2 ]
485773 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
486628 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959 ]
489050 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
489508 MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430 ] [EC:2.7.12.2 ]
490244 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X2 [KO:K04857 ]
490682 SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099 ]
491860 ELK1; ETS domain-containing protein Elk-1 [KO:K04375 ]
607007 HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523 ]
607269 CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183 ]
607357 ADCY1; LOW QUALITY PROTEIN: adenylate cyclase type 1 isoform X5 [KO:K08041 ] [EC:4.6.1.1 ]
610764 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515 ] [EC:2.7.11.17 ]
612941 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Ruf F, Sealfon SC.
Title Genomics view of gonadotrope signaling circuits.
Journal Reference Authors Harrison GS, Wierman ME, Nett TM, Glode LM.
Title Gonadotropin-releasing hormone and its receptor in normal and malignant cells.
Journal Reference Authors Pawson AJ, McNeilly AS.
Title The pituitary effects of GnRH.
Journal Reference Authors DeGroot LJ, Jameson JL (ed).
Title Endocrinology (Fifth edition)
Journal Elsevier Saunders (2006)
Reference 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 Reference Authors Ruf F, Fink MY, Sealfon SC.
Title Structure of the GnRH receptor-stimulated signaling network: insights from genomics.
Journal Reference 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 Reference Authors Shah BH, Catt KJ.
Title Matrix metalloproteinases in reproductive endocrinology.
Journal Reference 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 Reference Authors Naor Z
Title Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor.
Journal Related cfa04060 Cytokine-cytokine receptor interaction
cfa04080 Neuroactive ligand-receptor interaction
KO pathway 
