KEGG   PATHWAY: oda04922
Entry
oda04922                    Pathway                                
Name
Glucagon signaling pathway - Oryx dammah (scimitar-horned oryx)
Description
Glucagon is conventionally regarded as a counterregulatory hormone for insulin and plays a critical anti-hypoglycemic role by maintaining glucose homeostasis in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. Glucagon also stimulates hepatic mitochondrial beta-oxidation to supply energy for glucose production. Glucagon performs its main effect via activation of adenylate cyclase. The adenylate-cyclase-derived cAMP activates protein kinase A (PKA), which then phosphorylates downstream targets, such as cAMP response element binding protein (CREB) and the bifunctional enzyme 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase (one of the isoforms being PFK/FBPase 1, encoded by PFKFB1).
Class
Organismal Systems; Endocrine system
Pathway map
oda04922  Glucagon signaling pathway
oda04922

Organism
Oryx dammah (scimitar-horned oryx) [GN:oda]
Gene
120880303  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120875130  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
120872394  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
120876424  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
120854854  GCG; pro-glucagon isoform X1 [KO:K05259]
120866869  GCGR; glucagon receptor isoform X1 [KO:K04583]
120869377  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
120869379  neuroendocrine secretory protein 55 [KO:K04632]
120879368  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
120864090  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
120856949  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
120854564  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
120854293  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
120857618  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
120876928  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
120877626  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
120880365  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
120855782  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
120864822  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
120877414  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
120881698  PPP4R3C; protein PPP4R3C [KO:K17491]
120874997  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
120851829  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
120877071  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
120869894  LOW QUALITY PROTEIN: CREB-regulated transcription coactivator 2-like [KO:K16333]
120855778  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
120876224  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
120857601  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
120874330  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
120861984  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
120883093  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
120875860  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
120853216  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
120869193  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
120869195  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
120874626  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
120867669  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
120858499  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
120869823  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
120861873  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120865288  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120865483  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120851376  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
120864045  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
120877497  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
120861703  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
120863412  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
120865286  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
120883089  FOXO1; forkhead box protein O1 [KO:K07201]
120865204  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
120858467  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
120872122  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
120867120  G6PC1; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
120854888  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
120867042  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
120853458  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
120869363  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
120874135  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
120857792  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
120872120  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
120858929  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
120872161  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
120882529  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
120881977  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
120872913  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
120876938  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
120877899  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
120879484  calmodulin-1-like [KO:K02183]
120879826  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
120851742  CALM2; calmodulin-2 [KO:K02183]
120852515  calmodulin-like protein 4 isoform X1 [KO:K02183]
120860890  calmodulin-like protein 4 isoform X1 [KO:K02183]
120853084  calmodulin-1 [KO:K02183]
120869481  calmodulin-like [KO:K02183]
120853545  CALM1; calmodulin-1 isoform X1 [KO:K02183]
120872248  CALM3; calmodulin-3 [KO:K02183]
120858425  calmodulin-1-like [KO:K02183]
120853112  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
120869489  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
120874632  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
120882186  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
120879416  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
120856086  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
120871110  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
120855986  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
120877947  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
120861280  5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
120854364  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
120858195  5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
120866406  ACACA; acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
120871398  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
120856308  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
120869759  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
120877500  GCK; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
120866996  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
120867004  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
120861312  ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
120869458  ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
120856433  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
120858140  ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
120867909  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
120873837  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
120874473  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
120860842  pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
120853506  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
120882523  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
120861920  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
120867974  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
120858930  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
120862783  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
120870260  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
120874331  L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
120874332  L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
Compound
C00022  Pyruvate
C00024  Acetyl-CoA
C00026  2-Oxoglutarate
C00031  D-Glucose
C00036  Oxaloacetate
C00040  Acyl-CoA
C00042  Succinate
C00074  Phosphoenolpyruvate
C00076  Calcium cation
C00083  Malonyl-CoA
C00085  D-Fructose 6-phosphate
C00103  D-Glucose 1-phosphate
C00122  Fumarate
C00149  (S)-Malate
C00158  Citrate
C00182  Glycogen
C00186  (S)-Lactate
C00197  3-Phospho-D-glycerate
C00311  Isocitrate
C00354  D-Fructose 1,6-bisphosphate
C00575  3',5'-Cyclic AMP
C00631  2-Phospho-D-glycerate
C00665  beta-D-Fructose 2,6-bisphosphate
C00668  alpha-D-Glucose 6-phosphate
C01172  beta-D-Glucose 6-phosphate
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:12626323
  Authors
Jiang G, Zhang BB
  Title
Glucagon and regulation of glucose metabolism.
  Journal
Am J Physiol Endocrinol Metab 284:E671-8 (2003)
DOI:10.1152/ajpendo.00492.2002
Reference
PMID:24692138
  Authors
Rui L
  Title
Energy metabolism in the liver.
  Journal
Compr Physiol 4:177-97 (2014)
DOI:10.1002/cphy.c130024
Reference
PMID:22004992
  Authors
Jitrapakdee S
  Title
Transcription factors and coactivators controlling nutrient and hormonal regulation of hepatic gluconeogenesis.
  Journal
Int J Biochem Cell Biol 44:33-45 (2012)
DOI:10.1016/j.biocel.2011.10.001
Reference
PMID:16601267
  Authors
Desvergne B, Michalik L, Wahli W.
  Title
Transcriptional regulation of metabolism.
  Journal
Physiol Rev 86:465-514 (2006)
DOI:10.1152/physrev.00025.2005
Reference
PMID:22550228
  Authors
Hardie DG
  Title
Organismal carbohydrate and lipid homeostasis.
  Journal
Cold Spring Harb Perspect Biol 4:a006031 (2012)
DOI:10.1101/cshperspect.a006031
Reference
PMID:22796337
  Authors
Hasenour CM, Berglund ED, Wasserman DH
  Title
Emerging role of AMP-activated protein kinase in endocrine control of metabolism in the liver.
  Journal
Mol Cell Endocrinol 366:152-62 (2013)
DOI:10.1016/j.mce.2012.06.018
Reference
PMID:18669612
  Authors
Quesada I, Tuduri E, Ripoll C, Nadal A
  Title
Physiology of the pancreatic alpha-cell and glucagon secretion: role in glucose homeostasis and diabetes.
  Journal
J Endocrinol 199:5-19 (2008)
DOI:10.1677/JOE-08-0290
Reference
PMID:24238363
  Authors
Oh KJ, Han HS, Kim MJ, Koo SH
  Title
CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis.
  Journal
BMB Rep 46:567-74 (2013)
DOI:10.5483/BMBRep.2013.46.12.248
Reference
PMID:16479585
  Authors
Cheng A, Saltiel AR
  Title
More TORC for the gluconeogenic engine.
  Journal
Bioessays 28:231-4 (2006)
DOI:10.1002/bies.20375
Reference
PMID:21346730
  Authors
Altarejos JY, Montminy M
  Title
CREB and the CRTC co-activators: sensors for hormonal and metabolic signals.
  Journal
Nat Rev Mol Cell Biol 12:141-51 (2011)
DOI:10.1038/nrm3072
Reference
PMID:24393785
  Authors
Pernicova I, Korbonits M
  Title
Metformin--mode of action and clinical implications for diabetes and cancer.
  Journal
Nat Rev Endocrinol 10:143-56 (2014)
DOI:10.1038/nrendo.2013.256
Reference
PMID:20735177
  Authors
Hirota K, Fukamizu A
  Title
Transcriptional regulation of energy metabolism in the liver.
  Journal
J Recept Signal Transduct Res 30:403-9 (2010)
DOI:10.3109/10799893.2010.509730
Reference
PMID:21941300
  Authors
Chalkiadaki A, Guarente L
  Title
Metabolic signals regulate SIRT1 expression.
  Journal
EMBO Rep 12:985-6 (2011)
DOI:10.1038/embor.2011.179
Reference
PMID:22249520
  Authors
Chalkiadaki A, Guarente L
  Title
Sirtuins mediate mammalian metabolic responses to nutrient availability.
  Journal
Nat Rev Endocrinol 8:287-96 (2012)
DOI:10.1038/nrendo.2011.225
Reference
PMID:19912989
  Authors
Tang BL, Chua CE
  Title
Is systemic activation of Sirt1 beneficial for ageing-associated metabolic disorders?
  Journal
Biochem Biophys Res Commun 391:6-10 (2010)
DOI:10.1016/j.bbrc.2009.11.016
Reference
PMID:22503562
  Authors
Ozcan L, Wong CC, Li G, Xu T, Pajvani U, Park SK, Wronska A, Chen BX, Marks AR, Fukamizu A, Backs J, Singer HA, Yates JR 3rd, Accili D, Tabas I
  Title
Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity.
  Journal
Cell Metab 15:739-51 (2012)
DOI:10.1016/j.cmet.2012.03.002
Reference
PMID:22495310
  Authors
Wang Y, Li G, Goode J, Paz JC, Ouyang K, Screaton R, Fischer WH, Chen J, Tabas I, Montminy M
  Title
Inositol-1,4,5-trisphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes.
  Journal
Nature 485:128-32 (2012)
DOI:10.1038/nature10988
Related
pathway
oda00010  Glycolysis / Gluconeogenesis
oda00020  Citrate cycle (TCA cycle)
oda00061  Fatty acid biosynthesis
oda00190  Oxidative phosphorylation
oda04020  Calcium signaling pathway
oda04024  cAMP signaling pathway
oda04068  FoxO signaling pathway
oda04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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