KEGG   PATHWAY: bom04922
Entry
bom04922                    Pathway                                
Name
Glucagon signaling pathway - Bos mutus (wild yak)
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
bom04922  Glucagon signaling pathway
bom04922

Organism
Bos mutus (wild yak) [GN:bom]
Gene
102275199  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102265427  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102283212  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102285991  cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
102265240  GCG; glucagon [KO:K05259]
102283627  GCGR; glucagon receptor [KO:K04583]
102266153  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102286123  neuroendocrine secretory protein 55 [KO:K04632]
102274117  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102281757  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102269124  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102281756  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
102283891  ATF2; activating transcription factor 2 [KO:K04450]
102267423  ATF4; activating transcription factor 4 [KO:K04374]
102281505  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
102268154  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
102264680  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
102271999  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
102277321  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
102275204  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
102279982  PPP4R3B; protein phosphatase 4 regulatory subunit 3B [KO:K17491]
102284492  PPP4R3A; protein phosphatase 4 regulatory subunit 3A [KO:K17491]
102271057  PPP4C; protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
102280934  CRTC2; CREB regulated transcription coactivator 2 [KO:K16333]
102264410  SIK2; salt inducible kinase 2 [KO:K16311] [EC:2.7.11.1]
102264880  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
102273007  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
102275427  PPARGC1A; PPARG coactivator 1 alpha [KO:K07202]
102286910  SIK1; salt inducible kinase 1 [KO:K19008] [EC:2.7.11.1]
102287414  GNAQ; G protein subunit alpha q [KO:K04634]
102264989  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102278948  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102273347  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102276260  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102269088  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102269013  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102271039  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102275863  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102286752  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102266749  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102272271  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102277736  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102281822  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
102271451  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102279381  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102280002  calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
102284612  FOXO1; forkhead box O1 [KO:K07201]
102276604  SIRT1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
102284417  PPARA; peroxisome proliferator activated receptor alpha [KO:K07294]
102280048  PRMT1; protein arginine methyltransferase 1 [KO:K11434] [EC:2.1.1.319]
102275376  G6PC2; glucose-6-phosphatase catalytic subunit 2 [KO:K01084] [EC:3.1.3.9]
102288249  G6PC; glucose-6-phosphatase catalytic subunit [KO:K01084] [EC:3.1.3.9]
102276125  G6PC3; glucose-6-phosphatase catalytic subunit 3 [KO:K01084] [EC:3.1.3.9]
102271756  PCK1; phosphoenolpyruvate carboxykinase 1 [KO:K01596] [EC:4.1.1.32]
102265930  PCK2; phosphoenolpyruvate carboxykinase 2, mitochondrial [KO:K01596] [EC:4.1.1.32]
102265568  CPT1A; carnitine palmitoyltransferase 1A [KO:K08765] [EC:2.3.1.21]
102269192  CPT1B; carnitine palmitoyltransferase 1B [KO:K19523] [EC:2.3.1.21]
102287746  CPT1C; carnitine palmitoyltransferase 1C [KO:K19524] [EC:2.3.1.21]
102272943  GYS2; glycogen synthase 2 [KO:K00693] [EC:2.4.1.11]
102278988  GYS1; glycogen synthase 1 [KO:K00693] [EC:2.4.1.11]
102268378  PHKA2; phosphorylase kinase regulatory subunit alpha 2 [KO:K07190]
102271262  PHKA1; phosphorylase kinase regulatory subunit alpha 1 [KO:K07190]
102274220  phosphorylase b kinase regulatory subunit beta-like [KO:K07190]
102266225  PHKG1; phosphorylase kinase catalytic subunit gamma 1 [KO:K00871] [EC:2.7.11.19]
102279229  PHKG2; phosphorylase kinase catalytic subunit gamma 2 [KO:K00871] [EC:2.7.11.19]
102280361  calmodulin-alpha [KO:K02183]
102285968  CALML6; calmodulin like 6 [KO:K02183]
102281667  CALM1; calmodulin 1 [KO:K02183]
102287375  calmodulin [KO:K02183]
102268061  CALM2; calmodulin 2 [KO:K02183]
102265605  calmodulin-alpha [KO:K02183]
102266295  calmodulin [KO:K02183]
102282476  CALM3; calmodulin 3 [KO:K02183]
102269657  CALML3; calmodulin-like protein 3 [KO:K02183]
102271961  calmodulin-2/4-like [KO:K02183]
102284406  CALML4; calmodulin like 4 [KO:K02183]
102288373  PYGM; glycogen phosphorylase, muscle associated [KO:K00688] [EC:2.4.1.1]
102270861  PYGL; glycogen phosphorylase L [KO:K00688] [EC:2.4.1.1]
102268270  PYGB; glycogen phosphorylase B [KO:K00688] [EC:2.4.1.1]
102284536  6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
102266564  PFKFB1; 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
102270414  PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 [KO:K07198] [EC:2.7.11.31]
102265959  PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 [KO:K07198] [EC:2.7.11.31]
102278235  PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199]
102275377  PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199]
102276048  PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200]
102277941  PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 [KO:K07200]
102268424  PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200]
102284276  ACACA; acetyl-CoA carboxylase alpha [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
102275206  ACACB; acetyl-CoA carboxylase beta [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
102278454  SLC2A1; solute carrier family 2 member 1 [KO:K07299]
102277237  SLC2A2; solute carrier family 2 member 2 [KO:K07593]
102277785  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
102285847  FBP1; fructose-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
102270280  fructose-1,6-bisphosphatase isozyme 2-like [KO:K03841] [EC:3.1.3.11]
102269659  PFKP; phosphofructokinase, platelet [KO:K00850] [EC:2.7.1.11]
102285285  PFKM; phosphofructokinase, muscle [KO:K00850] [EC:2.7.1.11]
102268656  PFKL; phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
102271561  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
102286777  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
102272524  PGAM4; phosphoglycerate mutase family member 4 [KO:K01834] [EC:5.4.2.11]
102283146  PKM; pyruvate kinase, muscle [KO:K00873] [EC:2.7.1.40]
102286090  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
102275901  PDHA1; pyruvate dehydrogenase (lipoamide) alpha 1 [KO:K00161] [EC:1.2.4.1]
102287624  PDHB; pyruvate dehydrogenase (lipoamide) beta [KO:K00162] [EC:1.2.4.1]
102265127  LDHB; lactate dehydrogenase B [KO:K00016] [EC:1.1.1.27]
102274962  LDHA; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
102274105  LDHC; L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
102282411  LDHAL6B; lactate dehydrogenase A like 6B [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
bom00010  Glycolysis / Gluconeogenesis
bom00020  Citrate cycle (TCA cycle)
bom00061  Fatty acid biosynthesis
bom00190  Oxidative phosphorylation
bom04020  Calcium signaling pathway
bom04024  cAMP signaling pathway
bom04068  FoxO signaling pathway
bom04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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