KEGG   PATHWAY: tfn04922
Entry
tfn04922                    Pathway                                
Name
Glucagon signaling pathway - Trachypithecus francoisi (Francois's langur)
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
tfn04922  Glucagon signaling pathway
tfn04922

Organism
Trachypithecus francoisi (Francois's langur) [GN:tfn]
Gene
117071286  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117091956  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117076331  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117081551  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
117094944  GCG; glucagon [KO:K05259]
117066839  GCGR; glucagon receptor isoform X1 [KO:K04583]
117068997  neuroendocrine secretory protein 55 [KO:K04632]
117069000  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
117064735  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
117098498  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
117092158  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
117074523  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
117094598  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
117094833  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
117096463  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
117079895  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
117099006  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
117073578  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
117075642  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
117072944  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
117078272  PPP4R3C; LOW QUALITY PROTEIN: protein PPP4R3C [KO:K17491]
117071535  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
117099663  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
117087616  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
117097521  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 4 catalytic subunit-like [KO:K15423] [EC:3.1.3.16]
117065177  CRTC2; LOW QUALITY PROTEIN: CREB-regulated transcription coactivator 2 [KO:K16333]
117096425  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117097726  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
117085214  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
117095852  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
117098435  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
117070870  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
117080608  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
117068469  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
117068471  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
117083173  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
117090367  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
117087057  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
117064180  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
117082599  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
117093193  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
117098896  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
117099768  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
117081990  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
117073301  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
117065600  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
117085812  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
117097036  FOXO1; forkhead box protein O1 isoform X1 [KO:K07201]
117082466  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
117096318  PPARA; peroxisome proliferator-activated receptor alpha isoform X1 [KO:K07294]
117091592  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
117066897  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
117066932  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
117094898  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
117068976  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
117069918  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
117081475  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
117096247  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
117091589  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
117090404  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
117091538  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
117078452  PHKA2; LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit alpha, liver isoform [KO:K07190]
117087742  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
117077363  LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform-like [KO:K07190]
117087666  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
117073532  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
117083595  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
117069878  calmodulin-1-like [KO:K02183]
117079553  calmodulin-1-like [KO:K02183]
117070455  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
117070827  calmodulin-1 [KO:K02183]
117062348  CALM2; calmodulin-2 [KO:K02183]
117071553  CALM1; calmodulin-1 [KO:K02183]
117091446  CALM3; calmodulin-3 [KO:K02183]
117082197  CALML3; calmodulin-like protein 3 [KO:K02183]
117082198  CALML5; calmodulin-like protein 5 [KO:K02183]
117093967  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
117095064  calmodulin-1-like [KO:K02183]
117069659  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
117081421  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
117068347  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
117078254  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
117091972  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
117065053  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
117089314  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
117075492  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
117090183  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
117073087  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
117094511  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
117067361  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
117089443  ACACB; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
117092745  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
117083729  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
117073299  GCK; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
117062703  FBP1; fructose-1,6-bisphosphatase 1 isoform X1 [KO:K03841] [EC:3.1.3.11]
117062718  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
117090211  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
117082618  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
117094182  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
117069056  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
117073291  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
117095152  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
117070409  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
117078518  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
117086397  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
117083059  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
117070580  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
117079830  LDHAL6A; LOW QUALITY PROTEIN: L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
117070781  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
117098429  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
117071570  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
117090401  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
117081626  LDHC; L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
117081627  LDHA; L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
117083627  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
117076309  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
117076842  LOW QUALITY PROTEIN: 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
tfn00010  Glycolysis / Gluconeogenesis
tfn00020  Citrate cycle (TCA cycle)
tfn00061  Fatty acid biosynthesis
tfn00190  Oxidative phosphorylation
tfn04020  Calcium signaling pathway
tfn04024  cAMP signaling pathway
tfn04068  FoxO signaling pathway
tfn04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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