KEGG   PATHWAY: lav04922
Entry
lav04922                    Pathway                                
Name
Glucagon signaling pathway - Loxodonta africana (African savanna elephant)
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
lav04922  Glucagon signaling pathway
lav04922

Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100663184  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100657536  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100660187  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100660871  PDE3B; LOW QUALITY PROTEIN: cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
100676198  GCG; glucagon [KO:K05259]
100676918  GCGR; glucagon receptor [KO:K04583]
100655206  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
100669226  neuroendocrine secretory protein 55-like [KO:K04632]
100673570  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100656966  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100674245  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100675162  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100657989  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
100662521  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X2 [KO:K04374]
100653565  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100673694  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
100666211  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100670574  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
100677344  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
100675079  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
100664928  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X2 [KO:K17491]
100677294  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
100656145  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X3 [KO:K17491]
100655012  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X2 [KO:K15423] [EC:3.1.3.16]
100673108  CRTC2; CREB-regulated transcription coactivator 2 isoform X3 [KO:K16333]
100663250  SIK2; serine/threonine-protein kinase SIK2 [KO:K16311] [EC:2.7.11.1]
100661096  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
100663731  LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
100654985  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X2 [KO:K07202]
100671882  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
100656672  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100670617  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
100672435  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100668575  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100663829  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100665028  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100667845  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100659666  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100661626  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
100664832  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100677352  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111751572  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100668807  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
104846071  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
100653927  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100663321  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
100658516  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
100655740  FOXO1; forkhead box protein O1 [KO:K07201]
100667672  SIRT1; LOW QUALITY PROTEIN: NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
100657770  PPARA; peroxisome proliferator-activated receptor alpha isoform X1 [KO:K07294]
100677716  PRMT1; protein arginine N-methyltransferase 1 isoform X2 [KO:K11434] [EC:2.1.1.319]
100670402  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
100676625  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
100657260  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
100677220  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
100676836  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
100665922  CPT1A; LOW QUALITY PROTEIN: carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
100677247  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
100667001  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
100658178  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
100659799  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
100659362  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
100661354  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X3 [KO:K07190]
100662025  PHKB; phosphorylase b kinase regulatory subunit beta isoform X3 [KO:K07190]
100663820  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X2 [KO:K00871] [EC:2.7.11.19]
100660711  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
100663507  CALM1; calmodulin-1 [KO:K02183]
100664679  CALM2; calmodulin-2 [KO:K02183]
100657612  calmodulin [KO:K02183]
100669885  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
100658962  CALML3; calmodulin-like protein 3 [KO:K02183]
100658208  calmodulin [KO:K02183]
100661005  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
100661899  PYGL; LOW QUALITY PROTEIN: glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
100670338  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
100654072  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
100659413  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X2 [KO:K07198] [EC:2.7.11.31]
100671280  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
100665273  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
100676546  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
100669727  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200]
100675348  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
100672035  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
100656603  ACACA; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
100657186  ACACB; LOW QUALITY PROTEIN: acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
100677089  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
100669209  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
100658238  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
100676689  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
100657235  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
100660422  PFKL; LOW QUALITY PROTEIN: ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
100676111  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
100661148  PFKP; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
100672423  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
100657095  PGAM2; LOW QUALITY PROTEIN: phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
100676056  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
100653931  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
100660992  PDHA1; LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
100654022  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
100658459  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
100668729  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
100667269  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
100658577  L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
100667968  LDHC; 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
lav00010  Glycolysis / Gluconeogenesis
lav00020  Citrate cycle (TCA cycle)
lav00061  Fatty acid biosynthesis
lav00190  Oxidative phosphorylation
lav04020  Calcium signaling pathway
lav04024  cAMP signaling pathway
lav04068  FoxO signaling pathway
lav04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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