Erk/MAPK signaling, ephrin signaling, FGF signaling, p53, and RAR signaling. Blocking nFGFR1 signaling with FGFR1(SP-/NLS)(TK-) and/or activation with FGFR1(SP-/NLS) affected genes in pathways involved in neuronal functions, such as GABA receptor signaling, calcium, melatonin, LTP, and LTD (Table 3). Thus, loss of nFGFR1 and excessive nFGFR1 signaling lead directly to dysregulation of major developmental pathways.Table 3Ingenuity pathway analysis (IPA)—selected IPA identified pathways that were regulated during cAMP/BDNF/GDNF-induced neuronal programming (NPC vs. NCC) and genes affected by dominant negative nuclear FGFR1(SP-/NLS)TK-) or constitutively active nuclear FGFR1(SP-/NLS) (RNAseq)NPC vs. NCCNPC vs. NPC+ FGFR1(SP-/NLS) (TK-)NCC vs. NCC+ FGFR1(SP-/NLS) (TK-)NCC vs. NCC+ FGFR1(SP-/NLS)Wnt/β-cateninYesYescAMP signalingYesAxonal guidance signalingYesG-protein signalingYesYesPKA signalingYesYesNeuropathic pain signalingYesYesCorticotropin releasing hormone signalingYesProlactin signalingYesYesYesGlioma signalingYesGABA receptorsYesNos in neuronsYesVEGFYesSynaptic LT DepressionYesSynaptic LT PotentiationYesYesP2Y purinergic signalingYesYesYesaldosteroneYesYesCalcium signalingYesYesHIF1AYesYesGrowth Hormone signalingYesYesIL-8IL-8Clathrin endocytosisYesYesYesCatecholamine biosynthesisERBYesYesEGFRMelatonin signalingYesCXCR4YesGAP junction signalingYesYesEphrin receptor signalingYesESC pluripotencyYesYesYesEnosYesYesTR/RXRYesIL8YescitrulineYesMacrophages, fibroblasts inflamationYesYesRenin/AngiotensinYesYesHuntington Disease signalingYesYesendothelinEndothelinCREBCREBYesCatecholamine biosynthesisNotchNotchWnt/CaAgrinNeurotrophin/TRKYesTelomeraseCyclin cell cycleERK/MAPkinaseYesAMPK signalingYesGlucocorticoidYesYesP53YesFGF signalingYesYesGDNFYesEGF signalingYesActin cytoskeletonYesJak1,3IGFGlioma invasivenessYesIL-6,17aHMGBYesLPS-MAPKYesPDGFYesRAR signalingRAR activationDNA repairAcute myeloid leukemia signalingYesCCK/GastrinEMT transitionNF-kBnanogII-2,4,3,8,9,15,12,Wnt/GSK-3BetaNGFReelin in neuronsMelanocyte developmentMyc-apoptosisSTAT3PKCEpithelial adherence junctionCategories affected only in FGFR1(SP-/NLS)(TK-) or FGFR1(SP-/NLS) transfected cells are listed by names
