KEGG   PATHWAY: mcc04922
Entry
mcc04922                    Pathway                                
Name
Glucagon signaling pathway - Macaca mulatta (rhesus 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
mcc04922  Glucagon signaling pathway
mcc04922

Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
714717  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
697747  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
700591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
698954  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
705508  GCG; glucagon [KO:K05259]
714542  GCGR; glucagon receptor isoform X1 [KO:K04583]
694289  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
100424899  neuroendocrine secretory protein 55 [KO:K04632]
695328  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
709728  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
718632  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
700652  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
708717  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
699072  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
703965  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
714981  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
713391  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
696350  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
721825  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
715951  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
697718  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
701718  PPP4R3C; protein PPP4R3C [KO:K17491]
718961  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X9 [KO:K17491]
100428159  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A [KO:K17491]
708510  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
715908  CRTC2; CREB-regulated transcription coactivator 2 [KO:K16333]
711453  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
706258  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
704331  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
715762  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X3 [KO:K07202]
722303  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
705680  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
701951  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
718418  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
718387  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
717764  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
703669  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
708714  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
718040  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
706955  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
708233  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
709773  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
574258  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100428682  PPP3R1; calcineurin subunit B type 1 isoform X3 [KO:K06268]
705980  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
702504  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
706977  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X11 [KO:K04515] [EC:2.7.11.17]
710540  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
700030  FOXO1; forkhead box protein O1 [KO:K07201]
695682  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
613250  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
719419  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
712053  G6PC; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
709062  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
714276  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
714922  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
696207  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
709837  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
720697  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
719429  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X2 [KO:K19524] [EC:2.3.1.21]
574233  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
706152  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
694376  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
699764  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
716390  PHKB; phosphorylase b kinase regulatory subunit beta [KO:K07190]
703091  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
100423096  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
717686  calmodulin [KO:K02183]
698552  CALM1; calmodulin-1 isoform X1 [KO:K02183]
715270  CALM2; calmodulin-2 [KO:K02183]
703514  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
712159  CALML5; calmodulin-like protein 5 [KO:K02183]
722513  CALML3; calmodulin-like protein 3 [KO:K02183]
716584  CALM3; calmodulin-3 isoform X1 [KO:K02183]
693753  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
706351  calmodulin-like [KO:K02183]
706853  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
705777  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
717451  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
701969  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
695558  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
717703  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
695737  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
699806  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
702782  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X2 [KO:K07200]
709298  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
100425255  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
714218  ACACA; acetyl-CoA carboxylase 1 precursor [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
706909  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
698931  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
695538  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
699728  GCK; glucokinase isoform X1 [KO:K12407] [EC:2.7.1.2]
709022  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
100430821  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
707806  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
722330  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
722173  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
100430850  ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
694418  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
706211  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
696959  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
720615  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
714548  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
710798  pyruvate kinase PKM [KO:K00873] [EC:2.7.1.40]
697742  PKM; pyruvate kinase PKM isoform X2 [KO:K00873] [EC:2.7.1.40]
709359  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
100423990  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
574227  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
696854  LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
694309  LDHA; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
702403  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
693731  LDHC; L-lactate dehydrogenase C chain isoform X1 [KO:K00016] [EC:1.1.1.27]
693907  LDHAL6A; L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
706110  LDHB; L-lactate dehydrogenase B chain isoform LDHB [KO:K00016] [EC:1.1.1.27]
712268  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
  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
  Authors
Rui L
  Title
Energy metabolism in the liver.
  Journal
Compr Physiol 4:177-97 (2014)
DOI:10.1002/cphy.c130024
Reference
  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
  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
  Authors
Hardie DG
  Title
Organismal carbohydrate and lipid homeostasis.
  Journal
Cold Spring Harb Perspect Biol 4:a006031 (2012)
DOI:10.1101/cshperspect.a006031
Reference
  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
  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
  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
  Authors
Cheng A, Saltiel AR
  Title
More TORC for the gluconeogenic engine.
  Journal
Bioessays 28:231-4 (2006)
DOI:10.1002/bies.20375
Reference
  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
  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
  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
  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
  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
  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
  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
  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
mcc00010  Glycolysis / Gluconeogenesis
mcc00020  Citrate cycle (TCA cycle)
mcc00061  Fatty acid biosynthesis
mcc00190  Oxidative phosphorylation
mcc04020  Calcium signaling pathway
mcc04024  cAMP signaling pathway
mcc04068  FoxO signaling pathway
mcc04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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