KEGG   PATHWAY: etf04922
Entry
etf04922                    Pathway                                
Name
Glucagon signaling pathway - Echinops telfairi (small Madagascar hedgehog)
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
etf04922  Glucagon signaling pathway
etf04922

Organism
Echinops telfairi (small Madagascar hedgehog) [GN:etf]
Gene
101643102  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101649881  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101655315  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101653265  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
101651055  GCG; pro-glucagon [KO:K05259]
101647442  GCGR; glucagon receptor [KO:K04583]
101654894  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
101650626  neuroendocrine secretory protein 55 [KO:K04632]
101645045  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101649991  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101645802  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
101646557  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101656771  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101650311  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101653565  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101648900  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
101654666  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X2 [KO:K09048]
101654039  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X3 [KO:K09048]
101639977  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101648034  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
101658644  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
101649520  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X5 [KO:K17491]
101646639  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A [KO:K17491]
101647851  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
101653725  CRTC2; CREB-regulated transcription coactivator 2 [KO:K16333]
101642690  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
101641939  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101647070  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:2.3.1.48]
101653353  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
101647360  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
101637893  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101651304  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101650582  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101647679  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
101656854  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
101654141  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101638553  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101657031  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101639952  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
101642124  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
101638696  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101660901  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
101647023  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
101644337  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
101651457  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X3 [KO:K04515] [EC:2.7.11.17]
101664486  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101638605  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101661221  FOXO1; forkhead box protein O1 [KO:K07201]
101655735  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
101655834  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
101652312  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
101643287  G6PC2; LOW QUALITY PROTEIN: glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
101661828  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
101642368  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
101640119  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
101652483  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
101653715  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
101651337  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
101657954  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
101651083  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
101650073  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
101649142  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
101651797  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
101641208  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
101638911  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
101638689  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
115871000  calmodulin-A-like [KO:K02183]
101651650  neo-calmodulin-like [KO:K02183]
101662569  CALML6; calmodulin-like protein 6 [KO:K02183]
101656820  CALM3; calmodulin-3 [KO:K02183]
101638094  calmodulin-alpha-like [KO:K02183]
101650375  CALML3; calmodulin-like protein 3 [KO:K02183]
101662916  CALML5; calmodulin-like protein 5 [KO:K02183]
101654870  CALM1; calmodulin-1 [KO:K02183]
101649322  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
101643468  CALM2; calmodulin-2 [KO:K02183]
101651149  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
101660820  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
101648425  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
101656880  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
101642508  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X2 [KO:K07198] [EC:2.7.11.31]
101659697  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
101657327  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
101649263  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
101662226  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
101649172  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
101647774  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
101648265  ACACA; acetyl-CoA carboxylase 1 isoform X4 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101664465  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101659113  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
101656481  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
101638924  hexokinase-4 [KO:K12407] [EC:2.7.1.2]
101648213  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
101663147  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
101660140  ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
101653492  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
101641467  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
101662326  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
101644152  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
101654266  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
101650832  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
101656931  PKM; pyruvate kinase PKM [KO:K00873] [EC:2.7.1.40]
101650368  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X2 [KO:K00161] [EC:1.2.4.1]
101662434  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
101659257  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
101650016  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
101646393  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
101645051  LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
101639886  L-lactate dehydrogenase C chain-like [KO:K00016] [EC:1.1.1.27]
101657030  LDHAL6A; L-lactate dehydrogenase A-like 6A isoform X1 [KO:K00016] [EC:1.1.1.27]
101638010  L-lactate dehydrogenase B chain-like [KO:K00016] [EC:1.1.1.27]
101650384  LDHB; L-lactate dehydrogenase B 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
etf00010  Glycolysis / Gluconeogenesis
etf00020  Citrate cycle (TCA cycle)
etf00061  Fatty acid biosynthesis
etf00190  Oxidative phosphorylation
etf04020  Calcium signaling pathway
etf04024  cAMP signaling pathway
etf04068  FoxO signaling pathway
etf04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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