KEGG   PATHWAY: tge04922
Entry
tge04922                    Pathway                                
Name
Glucagon signaling pathway - Theropithecus gelada (gelada)
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
tge04922  Glucagon signaling pathway
tge04922

Organism
Theropithecus gelada (gelada) [GN:tge]
Gene
112629473  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112609286  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112612288  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
112606069  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
112635793  GCG; glucagon isoform X1 [KO:K05259]
112609753  GCGR; glucagon receptor [KO:K04583]
112632630  neuroendocrine secretory protein 55 [KO:K04632]
112632629  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
112625956  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
112608183  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
112618864  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
112612552  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
112636017  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
112636593  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
112632664  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
112620604  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
112613040  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
112607019  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
112636418  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
112608313  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
112621312  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
112629009  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
112616607  PPP4R3C; protein PPP4R3C [KO:K17491]
112604571  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
112614029  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
112636398  CRTC2; CREB-regulated transcription coactivator 2 [KO:K16333]
112605717  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
112614062  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
112632825  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
112624745  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
112621412  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
112607858  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
112607332  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
112633067  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
112633206  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
112627584  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
112618470  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
112634518  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
112622816  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
112630471  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
112631469  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
112624557  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
112608621  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
112604751  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
112621751  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
112631191  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
112624412  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
112625819  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
112610863  FOXO1; forkhead box protein O1 [KO:K07201]
112632129  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
112633545  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
112612900  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
112635835  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
112609342  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
112609747  G6PC; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
112629230  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
112632882  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
112606564  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
112632709  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
112611907  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
112613604  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
112634452  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
112614698  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
112615464  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
112615509  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform [KO:K07190]
112613788  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
112620149  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
112628492  CALM1; calmodulin-1 isoform X1 [KO:K02183]
112636897  CALM2; calmodulin-2 isoform X1 [KO:K02183]
112609174  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
112631384  calmodulin-like [KO:K02183]
112631589  CALML3; calmodulin-like protein 3 [KO:K02183]
112631867  CALML5; calmodulin-like protein 5 [KO:K02183]
112627411  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
112612423  CALM3; calmodulin-3 isoform X1 [KO:K02183]
112606600  PYGM; glycogen phosphorylase, muscle form isoform X1 [KO:K00688] [EC:2.4.1.1]
112628698  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
112632514  PYGB; glycogen phosphorylase, brain form isoform X1 [KO:K00688] [EC:2.4.1.1]
112615660  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
112613701  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
112626017  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
112618609  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
112634124  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
112620461  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
112636403  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
112634045  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
112609026  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
112635049  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
112630294  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
112618751  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
112620869  GCK; glucokinase isoform X1 [KO:K12407] [EC:2.7.1.2]
112607899  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
112608177  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
112617401  ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
112620269  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
112634756  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
112620964  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
112621296  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
112608399  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
112631276  PGAM1; phosphoglycerate mutase 1 isoform X1 [KO:K01834] [EC:5.4.2.11]
112632851  phosphoglycerate mutase 1-like isoform X1 [KO:K01834] [EC:5.4.2.11]
112635925  pyruvate kinase PKM-like isoform X1 [KO:K00873] [EC:2.7.1.40]
112627604  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
112615463  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
112625013  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
112605030  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
112617828  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial isoform X1 [KO:K00162] [EC:1.2.4.1]
112606355  LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
112606356  LDHC; L-lactate dehydrogenase C chain isoform X1 [KO:K00016] [EC:1.1.1.27]
112613909  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
112636501  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
112624787  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
112627364  LDHAL6B; L-lactate dehydrogenase A-like 6B isoform X1 [KO:K00016] [EC:1.1.1.27]
112605266  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
112634676  LDHB; L-lactate dehydrogenase B chain isoform X1 [KO:K00016] [EC:1.1.1.27]
112634809  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
112606119  LDHAL6A; L-lactate dehydrogenase A-like 6A [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
tge00010  Glycolysis / Gluconeogenesis
tge00020  Citrate cycle (TCA cycle)
tge00061  Fatty acid biosynthesis
tge00190  Oxidative phosphorylation
tge04020  Calcium signaling pathway
tge04024  cAMP signaling pathway
tge04068  FoxO signaling pathway
tge04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

DBGET integrated database retrieval system