KEGG   PATHWAY: mcoc04922
Entry
mcoc04922                   Pathway                                
Name
Glucagon signaling pathway - Mastomys coucha (southern multimammate mouse)
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
mcoc04922  Glucagon signaling pathway
mcoc04922

Organism
Mastomys coucha (southern multimammate mouse) [GN:mcoc]
Gene
116101889  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116104026  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116079779  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116102827  Pde3b; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
116092004  Gcg; glucagon [KO:K05259]
116077714  Gcgr; glucagon receptor isoform X1 [KO:K04583]
116091495  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
116091496  neuroendocrine secretory protein 55 [KO:K04632]
116083593  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
116093928  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116069698  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
116088513  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
116091666  Atf2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
116076129  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
116095903  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
116098735  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
116093212  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
116076210  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
116090490  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
116098936  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
116093494  protein PPP4R3C-like [KO:K17491]
116093527  protein PPP4R3C-like [KO:K17491]
116087094  protein PPP4R3C-like [KO:K17491]
116087217  LOW QUALITY PROTEIN: protein PPP4R3C-like [KO:K17491]
116069311  Ppp4r3b; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
116081187  Ppp4r3a; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
116102973  Ppp4c; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
116093209  Crtc2; CREB-regulated transcription coactivator 2 [KO:K16333]
116073309  Sik2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
116084175  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
116076368  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
116070819  Ppargc1a; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
116075048  Sik1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
116103624  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
116103465  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
116090695  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
116090998  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
116090999  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
116099362  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116099798  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116075536  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116093830  Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116084124  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116084832  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116096012  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
116071362  Ppp3r1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
116084777  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
116093748  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
116087223  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
116069264  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
116094452  Foxo1; forkhead box protein O1 [KO:K07201]
116075265  Sirt1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
116077376  Ppara; peroxisome proliferator-activated receptor alpha [KO:K07294]
116101220  Prmt1; protein arginine N-methyltransferase 1 [KO:K11434] [EC:2.1.1.319]
116076828  G6pc3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
116077838  G6pc; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
116092006  G6pc2; LOW QUALITY PROTEIN: glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
116092572  Pck1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
116084755  Pck2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
116103290  Cpt1a; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
116078025  Cpt1b; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
116102159  Cpt1c; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
116102200  Gys1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
116098429  Gys2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
116087327  Phka1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
116069775  Phkb; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
116090205  Phka2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
116103020  Phkg2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
116068481  Phkg1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
116102663  calmodulin-like [KO:K02183]
116101711  Calm3; calmodulin-3 [KO:K02183]
116082411  calmodulin-4 [KO:K02183]
116069997  calmodulin-like [KO:K02183]
116079808  Calm1; calmodulin-1 [KO:K02183]
116079993  Calm2; calmodulin-2 [KO:K02183]
116073523  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
116081777  calmodulin-like protein 3 [KO:K02183]
116103451  Pygm; glycogen phosphorylase, muscle form isoform X1 [KO:K00688] [EC:2.4.1.1]
116079987  Pygl; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
116091133  Pygb; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
116089485  Pfkfb1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
116096329  Prkaa2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
116083203  Prkaa1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
116093481  Prkab2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
116068264  Prkab1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
116097568  Prkag2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
116088583  Prkag3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
116079191  Prkag1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
116076883  Acaca; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
116068218  Acacb; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
116096528  Slc2a1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
116095027  Slc2a2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
116068614  Gck; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
116082329  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
116081758  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
116082742  Pfkp; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
116074891  Pfkl; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
116078880  Pfkm; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
116101454  Pgam1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
116069276  Pgam2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
116072132  Pkm; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
116099600  Pdha1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
116093861  Pdha2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
116072771  Pdhb; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
116102253  L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
116099763  Ldhb; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
116101223  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
116077221  Tmem242; transmembrane protein 242 [KO:K00016] [EC:1.1.1.27]
116088085  LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
116081783  L-lactate dehydrogenase A chain-like isoform X1 [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
mcoc00010  Glycolysis / Gluconeogenesis
mcoc00020  Citrate cycle (TCA cycle)
mcoc00061  Fatty acid biosynthesis
mcoc00190  Oxidative phosphorylation
mcoc04020  Calcium signaling pathway
mcoc04024  cAMP signaling pathway
mcoc04068  FoxO signaling pathway
mcoc04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

DBGET integrated database retrieval system