GnRH signaling pathway - Homo sapiens (human)

Curator(s): Joe Strothman

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.    
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GnRH signaling pathway - Homo sapiens (human) cluster_node33 !Hbegf cluster_node34 !Gnrh cluster_Membrane Membrane cluster_node35 !pg cluster_node36 !ca cluster_node37 !end cluster_node38 !map node2 1 matrix metallopeptidase 2 (gelatinase A,72kDa gelatinase,72kDa type IV collagenase) MMP2 MMP2->node2 MMP2 node4 HB-EGF MMP2->node4 MT1 MMP2->MT1 node5 9 node6 Ca 2+ CACN node6->CACN node7 1 node10 5 PKC PKC->node10 PKC node11 2 PKC->node11 v-raf-1 murine leukemia viral oncogene homolog 1 RAF1 PKC->RAF1 +p MEKK PKC->MEKK BMK PKC->BMK PLA2 PKC->PLA2 PLD PKC->PLD v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC PKC->SRC Pyk2 PKC->Pyk2 PKC->MT1 node11->PKC growth factor receptor-bound protein 2 GRB2 SOS GRB2->SOS node12 2 SOS->node12 SOS Ras SOS->Ras node13 1 Ras->node13 Ras Ras->RAF1 node14 2 RAF1->node14 RAF1 node26 MEK1/2 RAF1->node26 +p node15 1 PKA PKA->node15 PKA CREB PKA->CREB +p node16 1 CREB->node16 CREB DNA 1 CREB->DNA 1 node29 3 DNA 1->node29 CaMK CaMK->node29 node17 MKK3/6 MEKK->node17 +p p38MAPK node17->p38MAPK +p node18 1 p38MAPK->node18 p38MAPK p38MAPK->node29 node31 ? 1 BMK->node31 AA PLA2->AA node30 4 AA->node30 node19 PA, PE PLD->node19 node19->node30 node20 2 SRC->Ras SRC->node20 SRC cell division cycle 42 (GTP binding protein,25kDa) CDC42 SRC->CDC42 epidermal growth factor receptor EGFR SRC->EGFR +p mitogen-activated protein kinase kinase kinase 1 MAP3K1 CDC42->MAP3K1 node21 MKK4/7 JNK node21->JNK +p node22 11 JNK->node22 JNK node24 c-Jun JNK->node24 +p node23 1 node24->node23 c-Jun DNA 2 node24->DNA 2 DNA 2->node29 node32 ? 2 Pyk2->node32 node25 2 node26->node25 MEK1/2 node28 ERK1/2 node26->node28 +p node27 15 node28->node27 ERK1/2 ELK1,member of ETS oncogene family ELK1 node28->ELK1 +p DNA 3 ELK1->DNA 3 DNA 3->node29 node30->node29 follicle stimulating hormone,beta polypeptide FSHB node29->FSHB Gene expression node29->Gene expression Gonadotropins node29->Gonadotropins luteinizing hormone beta polypeptide LHB node29->LHB Secretion node29->Secretion aGSU node29->aGSU AC cAMP AC->cAMP cAMP->PKA CACN->node11 MAP3K1->node21 +p node9 Ca 2+ 2 node9->PKC CaM node9->CaM CaM->CaMK DAG DAG->PKC EGFR->node5 EGFR EGFR->GRB2 ER ER->node7 ER IP3R ER->IP3R IP3R->node9 node8 G q/11 PLCbeta node8->PLCbeta PLCbeta->DAG IP3 PLCbeta->IP3 gonadotropin-releasing hormone receptor GNRHR GNRHR->node8 Gs GNRHR->Gs Gs->AC GnRH GnRH->GNRHR node4->EGFR IP3->IP3R node3 Cytokine -cytokine receptor interaction - Homo sapiens node1 Neuroactive ligand-receptor interaction Calcium signaling pathway MAPK Signaling Pathway print "