KEGG   PATHWAY: oor04922
Entry
oor04922                    Pathway                                
Name
Glucagon signaling pathway - Orcinus orca (killer whale)
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
oor04922  Glucagon signaling pathway
oor04922

Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101272095  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101288103  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101273316  AKT1; RAC-alpha serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101270317  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B isoform X1 [KO:K13296] [EC:3.1.4.17]
101272149  GCG; pro-glucagon isoform X1 [KO:K05259]
101274122  GCGR; glucagon receptor isoform X8 [KO:K04583]
101286834  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
101282939  neuroendocrine secretory protein 55-like [KO:K04632]
101286207  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101272376  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101273911  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101287685  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
101276923  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X2 [KO:K04450]
101283438  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101283835  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101286338  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X3 [KO:K09048]
101272184  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
101284966  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101287411  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X2 [KO:K09048]
101289047  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X4 [KO:K09047]
101274400  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
101273945  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 4 regulatory subunit 3A-like [KO:K17491]
101287682  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
101276126  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
101269372  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
101287600  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
101276597  SIK2; serine/threonine-protein kinase SIK2 isoform X2 [KO:K16311] [EC:2.7.11.1]
101281894  CREBBP; CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
101287751  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101270017  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X2 [KO:K07202]
101284469  SIK1; serine/threonine-protein kinase SIK1 isoform X1 [KO:K19008] [EC:2.7.11.1]
101279781  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
101274558  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101270548  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101270961  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101281417  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X9 [KO:K05858] [EC:3.1.4.11]
101282737  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101281155  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101280894  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101271019  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
101278517  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X3 [KO:K04348] [EC:3.1.3.16]
101286888  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
105748080  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
101272877  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
101269181  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X16 [KO:K04515] [EC:2.7.11.17]
101287513  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X5 [KO:K04515] [EC:2.7.11.17]
101281498  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X8 [KO:K04515] [EC:2.7.11.17]
101271879  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101285637  FOXO1; forkhead box protein O1 [KO:K07201]
101279007  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X2 [KO:K11411] [EC:2.3.1.286]
101283267  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
101271584  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
101281224  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
101288353  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
101283146  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
101275401  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
101284360  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
101271948  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
101269413  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X2 [KO:K19523] [EC:2.3.1.21]
101271337  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
101287552  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
101284496  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
101270022  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X7 [KO:K07190]
101275570  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X2 [KO:K07190]
101288789  PHKB; phosphorylase b kinase regulatory subunit beta isoform X2 [KO:K07190]
101281573  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X2 [KO:K00871] [EC:2.7.11.19]
101270202  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X2 [KO:K00871] [EC:2.7.11.19]
101278649  CALML6; calmodulin-like protein 6 [KO:K02183]
101273078  CALM2; calmodulin-2 [KO:K02183]
101285814  CALM1; calmodulin-1 [KO:K02183]
101279979  CALM3; calmodulin-3 [KO:K02183]
101282017  calmodulin-alpha-like isoform X1 [KO:K02183]
105748632  LOW QUALITY PROTEIN: myosin light chain 1, skeletal muscle isoform-like [KO:K02183]
101284096  calmodulin-1-like [KO:K02183]
125961823  calmodulin-1-like [KO:K02183]
125961824  calmodulin-1-like [KO:K02183]
125961825  calmodulin-1-like [KO:K02183]
125961826  calmodulin-1-like [KO:K02183]
125961827  calmodulin-1-like [KO:K02183]
125961828  calmodulin-1-like [KO:K02183]
101269285  PYGL; glycogen phosphorylase, liver form isoform X2 [KO:K00688] [EC:2.4.1.1]
101279103  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
101287131  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
101282882  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X2 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
101287451  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
101290391  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
101270605  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X2 [KO:K07199]
101289338  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
101286740  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
101269890  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200]
101288264  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
101277103  ACACA; acetyl-CoA carboxylase 1 isoform X4 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101272632  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101272071  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X2 [KO:K07299]
101285939  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
101286839  GCK; hexokinase-4 isoform X6 [KO:K12407] [EC:2.7.1.2]
101285491  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
101285747  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
101282752  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
101275606  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X3 [KO:K00850] [EC:2.7.1.11]
101284216  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
101269619  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
101274638  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
101276272  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
101271664  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
101288495  PDHA2; LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
101287798  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial isoform X1 [KO:K00162] [EC:1.2.4.1]
101287134  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
101282118  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
101273820  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
101272057  LDHA; L-lactate dehydrogenase A chain isoform X2 [KO:K00016] [EC:1.1.1.27]
101272816  L-lactate dehydrogenase C chain [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
oor00010  Glycolysis / Gluconeogenesis
oor00020  Citrate cycle (TCA cycle)
oor00061  Fatty acid biosynthesis
oor00190  Oxidative phosphorylation
oor04020  Calcium signaling pathway
oor04024  cAMP signaling pathway
oor04068  FoxO signaling pathway
oor04910  Insulin signaling pathway
KO pathway
ko04922   
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