KEGG   PATHWAY: clud04922
Entry
clud04922                   Pathway                                
Name
Glucagon signaling pathway - Canis lupus dingo (dingo)
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
clud04922  Glucagon signaling pathway
clud04922

Organism
Canis lupus dingo (dingo) [GN:clud]
Gene
112658031  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112648737  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112645463  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112667669  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
112674677  GCG; pro-glucagon isoform X1 [KO:K05259]
112672942  GCGR; glucagon receptor isoform X2 [KO:K04583]
112674185  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
112674186  neuroendocrine secretory protein 55 [KO:K04632]
112662652  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
112666620  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
112640987  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
112656471  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
112668134  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
112667576  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
112647736  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
112670436  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
112650165  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
112663293  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
112666968  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
112670641  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
112656911  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
112672451  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
112654500  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
112640052  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
112647744  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
112671355  SIK2; serine/threonine-protein kinase SIK2 [KO:K16311] [EC:2.7.11.1]
112667202  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
112640446  CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
112654092  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
112669189  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
112644686  guanine nucleotide-binding protein G(q) subunit alpha isoform X2 [KO:K04634]
112659377  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
112673608  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
112673609  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
112676127  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X5 [KO:K05858] [EC:3.1.4.11]
112662581  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
112665544  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
112641421  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X3 [KO:K04960]
112644642  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
112669758  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
112651490  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
112650031  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
112673922  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
112671686  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
112650738  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X2 [KO:K04515] [EC:2.7.11.17]
112651229  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
112651948  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
112669362  FOXO1; forkhead box protein O1 [KO:K07201]
112651335  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
112665976  PPARA; peroxisome proliferator-activated receptor alpha isoform X1 [KO:K07294]
112645136  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
112655217  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
112655440  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
112668280  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
112657245  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
112674170  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
112659228  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
112665387  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X3 [KO:K19523] [EC:2.3.1.21]
112645134  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
112645175  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
112665506  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
112660557  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
112671847  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
112653713  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
112646074  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
112640112  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
112655674  calmodulin-1-like [KO:K02183]
112645263  CALM3; calmodulin-3 isoform X1 [KO:K02183]
112656898  CALM1; calmodulin-1 [KO:K02183]
112658063  calmodulin-1-like [KO:K02183]
112659069  CALML5; calmodulin-like protein 5 [KO:K02183]
112646988  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
112671784  CALM2; calmodulin-2 isoform X3 [KO:K02183]
112675698  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
112659017  calmodulin-like protein 3 [KO:K02183]
112656863  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
112668849  PYGB; glycogen phosphorylase, brain form isoform X1 [KO:K00688] [EC:2.4.1.1]
112659381  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
112673055  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X2 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
112647094  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
112652680  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
112664082  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X2 [KO:K07199]
112676653  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
112656757  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X3 [KO:K07200]
112678282  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X3 [KO:K07200]
112663432  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
112655082  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
112676715  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
112642247  SLC2A1; LOW QUALITY PROTEIN: solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
112645960  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
112650698  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
112644609  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
112644610  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
112678251  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
112669209  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
112659098  ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
112646097  LOW QUALITY PROTEIN: ATP-dependent 6-phosphofructokinase, muscle type-like [KO:K00850] [EC:2.7.1.11]
112672135  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
112650593  PGAM2; phosphoglycerate mutase 2 isoform X1 [KO:K01834] [EC:5.4.2.11]
112675646  PKM; pyruvate kinase PKM isoform X2 [KO:K00873] [EC:2.7.1.40]
112644274  PDHA2; LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
112653806  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
112665977  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial isoform X1 [KO:K00162] [EC:1.2.4.1]
112644351  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
112657190  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
112667722  LDHA; L-lactate dehydrogenase A chain isoform X2 [KO:K00016] [EC:1.1.1.27]
112667723  L-lactate dehydrogenase C chain isoform X1 [KO:K00016] [EC:1.1.1.27]
112678459  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
112649398  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
112662359  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
112651742  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
112665507  LDHB; L-lactate dehydrogenase B chain isoform X1 [KO:K00016] [EC:1.1.1.27]
112678754  LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
112673323  LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
112644163  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
112678374  L-lactate dehydrogenase A chain-like [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
clud00010  Glycolysis / Gluconeogenesis
clud00020  Citrate cycle (TCA cycle)
clud00061  Fatty acid biosynthesis
clud00190  Oxidative phosphorylation
clud04020  Calcium signaling pathway
clud04024  cAMP signaling pathway
clud04068  FoxO signaling pathway
clud04910  Insulin signaling pathway
KO pathway
ko04922   
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