KEGG   PATHWAY: cjc04922
Entry
cjc04922                    Pathway                                
Name
Glucagon signaling pathway - Callithrix jacchus (white-tufted-ear marmoset)
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
cjc04922  Glucagon signaling pathway
cjc04922

Organism
Callithrix jacchus (white-tufted-ear marmoset) [GN:cjc]
Gene
100404447  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100399039  AKT3; RAC-gamma serine/threonine-protein kinase isoform X6 [KO:K04456] [EC:2.7.11.1]
100388080  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100393923  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B isoform X8 [KO:K13296] [EC:3.1.4.17]
100399074  GCG; pro-glucagon [KO:K05259]
100390029  GCGR; glucagon receptor isoform X1 [KO:K04583]
100408515  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
103787209  neuroendocrine secretory protein 55 [KO:K04632]
100385658  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100392123  PRKACG; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
100408115  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
100407692  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100400737  PRKACA; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100409206  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
118151333  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
100407681  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100414156  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
100392193  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100394351  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
100408954  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
100406635  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
100411140  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
100409637  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
100392579  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X6 [KO:K09047]
100390906  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
100400223  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X6 [KO:K17491]
100394593  PPP4R3C; protein PPP4R3C [KO:K17491]
100393931  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
103789006  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
100395360  SIK2; serine/threonine-protein kinase SIK2 [KO:K16311] [EC:2.7.11.1]
100395278  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100405037  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
100411258  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X4 [KO:K07202]
100415569  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
100403006  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X2 [KO:K04634]
100400803  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100386921  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
100409716  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
100410075  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
100385763  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
118144170  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
100390843  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
100386369  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
100387059  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
100386452  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X5 [KO:K04348] [EC:3.1.3.16]
100392986  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100388148  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100397956  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X9 [KO:K04515] [EC:2.7.11.17]
100405903  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100391424  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:2.7.11.17]
100390938  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
100410352  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X4 [KO:K04515] [EC:2.7.11.17]
100397393  FOXO1; forkhead box protein O1 [KO:K07201]
100395149  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
100415661  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
100390972  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
100415213  G6PC1; glucose-6-phosphatase catalytic subunit 1 isoform X1 [KO:K01084] [EC:3.1.3.9]
100400291  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
100400025  G6PC3; glucose-6-phosphatase 3 isoform X2 [KO:K01084] [EC:3.1.3.9]
100404441  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
100404870  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X2 [KO:K01596] [EC:4.1.1.32]
100403111  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
100403864  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
100391686  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X3 [KO:K19524] [EC:2.3.1.21]
100406574  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
118144197  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
100395554  PHKB; phosphorylase b kinase regulatory subunit beta isoform X2 [KO:K07190]
100396892  PHKA1; LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
100397253  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
100412760  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
100414478  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X2 [KO:K00871] [EC:2.7.11.19]
100390180  CALM1; calmodulin-1 [KO:K02183]
100386819  CALM2; calmodulin-2 isoform X2 [KO:K02183]
100406081  CALM3; calmodulin-3 [KO:K02183]
100408289  CALML3; calmodulin-like protein 3 [KO:K02183]
100392199  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
100396690  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
108592443  CALML5; calmodulin-like protein 5 [KO:K02183]
118148021  calmodulin-1-like [KO:K02183]
100415749  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
100404453  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
100409115  PYGB; glycogen phosphorylase, brain form isoform X2 [KO:K00688] [EC:2.4.1.1]
100412706  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X7 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
100396565  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
100385413  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
100406673  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X3 [KO:K07199]
100409760  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
100394141  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X5 [KO:K07200]
100386781  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X6 [KO:K07200]
100390042  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
100397258  ACACA; acetyl-CoA carboxylase 1 isoform X2 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
100402980  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
100404544  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
100397713  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
100409392  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
100408581  FBP2; fructose-1,6-bisphosphatase isozyme 2 isoform X1 [KO:K03841] [EC:3.1.3.11]
100408949  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
100393627  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
100403074  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X2 [KO:K00850] [EC:2.7.1.11]
100403092  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
100407214  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
100400929  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
100413092  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
100412392  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
100389879  pyruvate kinase PKM-like [KO:K00873] [EC:2.7.1.40]
100403644  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
100400144  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
100403745  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
100397634  LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit beta, mitochondrial-like [KO:K00162] [EC:1.2.4.1]
100388121  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
100404572  LDHA; LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
100405170  LDHC; L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
100385261  LDHAL6A; L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
100399416  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
100415308  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
100896310  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
118142861  LDHB; L-lactate dehydrogenase B chain isoform X2 [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
cjc00010  Glycolysis / Gluconeogenesis
cjc00020  Citrate cycle (TCA cycle)
cjc00061  Fatty acid biosynthesis
cjc00190  Oxidative phosphorylation
cjc04020  Calcium signaling pathway
cjc04024  cAMP signaling pathway
cjc04068  FoxO signaling pathway
cjc04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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