KEGG   PATHWAY: pale04922
Entry
pale04922                   Pathway                                
Name
Glucagon signaling pathway - Pteropus alecto (black flying fox)
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
pale04922  Glucagon signaling pathway
pale04922

Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102894289  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
102887866  GCG; glucagon isoform X1 [KO:K05259]
102889146  GCGR; glucagon receptor [KO:K04583]
102889764  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102884106  neuroendocrine secretory protein 55-like [KO:K04632]
102893265  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102886679  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102877853  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102888198  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102889014  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
102896553  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102878515  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
102894633  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
102882888  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
102886510  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
102879289  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
102884583  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
102886393  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
102886799  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
102895206  serine/threonine-protein phosphatase 4 regulatory subunit 3B [KO:K17491]
102891141  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
102879203  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
102888580  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
102886172  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102881042  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102879270  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
102881656  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
102877919  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102879238  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102885207  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102885781  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102885953  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102894982  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102896356  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102881783  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102880029  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102883156  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102898473  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102894471  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
102895490  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102888982  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
102888385  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102880869  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
102896030  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
102892244  FOXO1; forkhead box protein O1 [KO:K07201]
102880351  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
102878006  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
102878450  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
102887492  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
102896886  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
102898137  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
102888528  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
102897596  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
102886073  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
102879520  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X2 [KO:K19523] [EC:2.3.1.21]
102878033  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
102890809  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
102884634  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
102879995  PHKB; LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit beta [KO:K07190]
102882713  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
102892742  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
102879938  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X2 [KO:K00871] [EC:2.7.11.19]
102882222  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X2 [KO:K00871] [EC:2.7.11.19]
102894226  CALM2; calmodulin-2 isoform X1 [KO:K02183]
102897273  CALM3; calmodulin-3 [KO:K02183]
102886058  CALM1; calmodulin-1 [KO:K02183]
102884196  CALML6; calmodulin-like protein 6 [KO:K02183]
102891673  calmodulin-like [KO:K02183]
102893109  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
102881744  calmodulin-like [KO:K02183]
102887527  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
102897270  PYGM; glycogen phosphorylase, muscle form isoform X2 [KO:K00688] [EC:2.4.1.1]
102878850  PYGB; glycogen phosphorylase, brain form isoform X1 [KO:K00688] [EC:2.4.1.1]
102897563  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
102884524  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
102886520  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
102886980  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
102887949  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
102898038  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
102882613  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X3 [KO:K07200]
102887347  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200]
102895052  ACACA; acetyl-CoA carboxylase 1 isoform X3 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
102887451  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
102885620  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
102883555  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
102884319  GCK; LOW QUALITY PROTEIN: glucokinase [KO:K12407] [EC:2.7.1.2]
102882419  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
102882663  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
102894946  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
102886089  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X3 [KO:K00850] [EC:2.7.1.11]
102893676  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
102887139  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
102883647  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
102879367  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
102897181  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
102882467  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
102884762  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
102891052  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
102887737  LDHA; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
102887989  LOW QUALITY PROTEIN: L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
102895089  LDHAL6B; L-lactate dehydrogenase A-like 6B [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
pale00010  Glycolysis / Gluconeogenesis
pale00020  Citrate cycle (TCA cycle)
pale00061  Fatty acid biosynthesis
pale00190  Oxidative phosphorylation
pale04020  Calcium signaling pathway
pale04024  cAMP signaling pathway
pale04068  FoxO signaling pathway
pale04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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