KEGG   PATHWAY: csab04922
Entry
csab04922                   Pathway                                
Name
Glucagon signaling pathway - Chlorocebus sabaeus (green monkey)
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
csab04922  Glucagon signaling pathway
csab04922

Organism
Chlorocebus sabaeus (green monkey) [GN:csab]
Gene
103234702  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103230869  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103229784  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103239798  PDE3B; phosphodiesterase 3B [KO:K13296] [EC:3.1.4.17]
103217184  GCG; glucagon [KO:K05259]
103243730  GCGR; glucagon receptor [KO:K04583]
103243509  GNAS; GNAS complex locus [KO:K04632]
103243499  neuroendocrine secretory protein 55 [KO:K04632]
103214981  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
103219549  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
103224540  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103234377  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
103217717  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
103217363  ATF2; activating transcription factor 2 [KO:K04450]
103223345  ATF4; activating transcription factor 4 [KO:K04374]
103236571  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
103223942  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
103226974  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
103233716  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
103219209  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
103226299  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
103231745  putative SMEK homolog 3 [KO:K17491]
103229557  PPP4R3A; protein phosphatase 4 regulatory subunit 3A [KO:K17491]
103220234  PPP4R3B; protein phosphatase 4 regulatory subunit 3B [KO:K17491]
103230568  PPP4C; protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
103223939  CRTC2; CREB regulated transcription coactivator 2 [KO:K16333]
103248443  SIK2; salt inducible kinase 2 [KO:K16311] [EC:2.7.11.1]
103231770  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
103223371  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
103246278  PPARGC1A; PPARG coactivator 1 alpha [KO:K07202]
103219558  SIK1; salt inducible kinase 1 [KO:K19008] [EC:2.7.11.1]
103219624  GNAQ; G protein subunit alpha q [KO:K04634]
103233299  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103246591  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103246657  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
103245842  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103227941  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103218776  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103221654  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103236040  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
103215997  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
103215459  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
103220127  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
103219106  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
103236144  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
103215984  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
103226136  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
103244792  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
103214322  FOXO1; forkhead box O1 [KO:K07201]
103216104  SIRT1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
103223491  PPARA; peroxisome proliferator activated receptor alpha [KO:K07294]
103235542  PRMT1; protein arginine methyltransferase 1 [KO:K11434] [EC:2.1.1.319]
103243337  G6PC3; glucose-6-phosphatase catalytic subunit 3 [KO:K01084] [EC:3.1.3.9]
103243379  G6PC; glucose-6-phosphatase catalytic subunit [KO:K01084] [EC:3.1.3.9]
103217259  G6PC2; glucose-6-phosphatase catalytic subunit 2 [KO:K01084] [EC:3.1.3.9]
103228704  PCK2; phosphoenolpyruvate carboxykinase 2, mitochondrial [KO:K01596] [EC:4.1.1.32]
103243712  PCK1; phosphoenolpyruvate carboxykinase 1 [KO:K01596] [EC:4.1.1.32]
103248480  CPT1A; carnitine palmitoyltransferase 1A [KO:K08765] [EC:2.3.1.21]
103223575  CPT1B; carnitine palmitoyltransferase 1B [KO:K19523] [EC:2.3.1.21]
103235051  CPT1C; carnitine palmitoyltransferase 1C [KO:K19524] [EC:2.3.1.21]
103235009  GYS1; glycogen synthase 1 [KO:K00693] [EC:2.4.1.11]
103218736  GYS2; glycogen synthase 2 [KO:K00693] [EC:2.4.1.11]
103231681  PHKA2; phosphorylase kinase regulatory subunit alpha 2 [KO:K07190]
103232181  PHKA1; phosphorylase kinase regulatory subunit alpha 1 [KO:K07190]
103232332  PHKB; phosphorylase kinase regulatory subunit beta [KO:K07190]
103231924  PHKG2; phosphorylase kinase catalytic subunit gamma 2 [KO:K00871] [EC:2.7.11.19]
103226033  PHKG1; phosphorylase kinase catalytic subunit gamma 1 [KO:K00871] [EC:2.7.11.19]
103245424  CALML4; calmodulin like 4 [KO:K02183]
103237820  CALML5; calmodulin like 5 [KO:K02183]
103237822  CALML3; calmodulin like 3 [KO:K02183]
103229541  CALM1; calmodulin 1 [KO:K02183]
103234915  CALM3; calmodulin 3 [KO:K02183]
103220326  CALM2; calmodulin 2 [KO:K02183]
103233110  PYGM; glycogen phosphorylase, muscle associated [KO:K00688] [EC:2.4.1.1]
103247035  PYGB; glycogen phosphorylase B [KO:K00688] [EC:2.4.1.1]
103228970  PYGL; glycogen phosphorylase L [KO:K00688] [EC:2.4.1.1]
103232032  PFKFB1; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
103215177  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
103224740  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
103247234  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
103239238  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
103227261  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
103238254  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
103217881  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
103242788  ACACA; acetyl-CoA carboxylase alpha [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
103239081  ACACB; acetyl-CoA carboxylase beta [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
103224987  SLC2A1; solute carrier family 2 member 1 [KO:K07299]
103221255  SLC2A2; solute carrier family 2 member 2 [KO:K07593]
103226145  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
103219839  FBP1; fructose-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
103219840  FBP2; fructose-bisphosphatase 2 [KO:K03841] [EC:3.1.3.11]
103237780  PFKP; phosphofructokinase, platelet [KO:K00850] [EC:2.7.1.11]
103219799  PFKL; phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
103238217  PFKM; phosphofructokinase, muscle [KO:K00850] [EC:2.7.1.11]
103231516  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
103216341  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
103227967  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
103226147  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
103230363  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
103226062  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
103216807  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
103246072  PKM; pyruvate kinase, muscle [KO:K00873] [EC:2.7.1.40]
103217002  pyruvate kinase PKM [KO:K00873] [EC:2.7.1.40]
103231682  PDHA1; pyruvate dehydrogenase (lipoamide) alpha 1 [KO:K00161] [EC:1.2.4.1]
103235992  PDHA2; pyruvate dehydrogenase (lipoamide) alpha 2 [KO:K00161] [EC:1.2.4.1]
103227812  PDHB; pyruvate dehydrogenase (lipoamide) beta [KO:K00162] [EC:1.2.4.1]
103239109  LDHAL6A; lactate dehydrogenase A like 6A [KO:K00016] [EC:1.1.1.27]
103239176  LDHA; lactate dehydrogenase A [KO:K00016] [EC:1.1.1.27]
103239190  LDHC; lactate dehydrogenase C [KO:K00016] [EC:1.1.1.27]
103245546  LDHAL6B; lactate dehydrogenase A like 6B [KO:K00016] [EC:1.1.1.27]
103217070  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
103218738  LDHB; lactate dehydrogenase B [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
csab00010  Glycolysis / Gluconeogenesis
csab00020  Citrate cycle (TCA cycle)
csab00061  Fatty acid biosynthesis
csab00190  Oxidative phosphorylation
csab04020  Calcium signaling pathway
csab04024  cAMP signaling pathway
csab04068  FoxO signaling pathway
csab04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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