KEGG   PATHWAY: eju04922
Entry
eju04922                    Pathway                                
Name
Glucagon signaling pathway - Eumetopias jubatus (Steller sea lion)
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
eju04922  Glucagon signaling pathway
eju04922

Organism
Eumetopias jubatus (Steller sea lion) [GN:eju]
Gene
114203265  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114203268  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114206518  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114215523  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114219342  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
114216514  GCG; glucagon isoform X1 [KO:K05259]
114216272  GCGR; glucagon receptor [KO:K04583]
114197913  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
114197962  neuroendocrine secretory protein 55 [KO:K04632]
114223681  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
114208397  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114197723  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114215964  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
114224124  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
114218458  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114218277  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
114226347  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
114211711  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
114198708  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
114215177  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
114221152  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
114209747  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
114205030  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
114197586  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
114214477  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
114198645  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
114211330  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
114218518  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
114219895  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
114197341  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
114226449  SIK1; serine/threonine-protein kinase SIK1 isoform X1 [KO:K19008] [EC:2.7.11.1]
114198742  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
114216386  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
114216392  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
114220426  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
114221305  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
114207665  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
114216613  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
114222155  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
114217489  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114201320  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114214123  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114218910  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
114213552  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
114202281  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
114211871  calcium/calmodulin-dependent protein kinase type II subunit alpha-like [KO:K04515] [EC:2.7.11.17]
114211898  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
114214078  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
114222643  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
114210547  FOXO1; forkhead box protein O1 [KO:K07201]
114214155  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
114218347  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
114199640  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
114200576  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
114201342  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
114222728  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
114217895  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
114197938  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
114220165  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
114218406  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
114199644  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
114216642  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
114199538  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
114207484  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
114199371  PHKB; phosphorylase b kinase regulatory subunit beta [KO:K07190]
114223602  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
114214357  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
114214412  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
114209406  calmodulin-like [KO:K02183]
114209774  CALM2; calmodulin-2 [KO:K02183]
114217752  calmodulin-like [KO:K02183]
114217770  LOW QUALITY PROTEIN: calmodulin-like protein 3 [KO:K02183]
114218775  calmodulin-like [KO:K02183]
114213217  CALML6; calmodulin-like protein 6 [KO:K02183]
114197096  CALM3; calmodulin-3 [KO:K02183]
114197118  calmodulin-like [KO:K02183]
114204978  CALM1; calmodulin-1 [KO:K02183]
114206437  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
114224509  PYGB; glycogen phosphorylase, brain form isoform X1 [KO:K00688] [EC:2.4.1.1]
114212728  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
114220481  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
114200781  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
114212116  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
114204800  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
114219011  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
114203347  5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
114203348  5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
114200181  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
114225812  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
114197984  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
114213809  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
114219120  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
114224204  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
114207055  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
114202278  GCK; glucokinase isoform X1 [KO:K12407] [EC:2.7.1.2]
114223354  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
114223384  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
114224062  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
114217731  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
114226395  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
114202270  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
114205296  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
114206544  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
114220134  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
114223582  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
114214674  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
114200222  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
114208265  L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
114216646  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
114200796  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
114209302  L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
114209517  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
114209521  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
114217474  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
114209852  L-lactate dehydrogenase A-like 6B isoform X1 [KO:K00016] [EC:1.1.1.27]
114210741  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
114211052  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
114202952  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
114219980  LDHAL6A; LOW QUALITY PROTEIN: L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
114219984  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
114219994  LDHC; L-lactate dehydrogenase C chain isoform X1 [KO:K00016] [EC:1.1.1.27]
114220974  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
114221019  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
114222152  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
114207015  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
114207406  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
114215902  L-lactate dehydrogenase A chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
114223980  L-lactate dehydrogenase B 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
eju00010  Glycolysis / Gluconeogenesis
eju00020  Citrate cycle (TCA cycle)
eju00061  Fatty acid biosynthesis
eju00190  Oxidative phosphorylation
eju04020  Calcium signaling pathway
eju04024  cAMP signaling pathway
eju04068  FoxO signaling pathway
eju04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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