KEGG   PATHWAY: oas04922
Entry
oas04922                    Pathway                                
Name
Glucagon signaling pathway - Ovis aries (sheep)
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
oas04922  Glucagon signaling pathway
oas04922

Organism
Ovis aries (sheep) [GN:oas]
Gene
101118462  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101119242  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100294652  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101121291  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B isoform X1 [KO:K13296] [EC:3.1.4.17]
443179  GCG; pro-glucagon isoform X1 [KO:K05259]
101115976  GCGR; glucagon receptor isoform X2 [KO:K04583]
101115640  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X5 [KO:K04632]
101102411  neuroendocrine secretory protein 55 [KO:K04632]
101102089  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
443094  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101108785  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
443118  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101108548  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
100216465  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101107485  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048]
101114243  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101108743  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101113586  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
101113882  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101112976  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
101121161  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
101111749  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X2 [KO:K17491]
101110823  serine/threonine-protein phosphatase 4 regulatory subunit 3-B-like [KO:K17491]
101115751  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
101102117  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
101107630  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
101110136  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
101123600  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
443270  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
101122497  SIK1; serine/threonine-protein kinase SIK1 isoform X1 [KO:K19008] [EC:2.7.11.1]
101112295  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101103585  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101113074  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101116105  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101106864  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X9 [KO:K05858] [EC:3.1.4.11]
101108864  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X4 [KO:K04958]
101113317  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
114109674  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
101108104  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
101115429  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
101122602  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
101120802  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
114108765  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
443453  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101113850  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X4 [KO:K04515] [EC:2.7.11.17]
101108884  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X10 [KO:K04515] [EC:2.7.11.17]
101118870  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101107877  FOXO1; forkhead box protein O1 [KO:K07201]
101102956  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
443457  PPARA; peroxisome proliferator-activated receptor alpha isoform X2 [KO:K07294]
100037687  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
101113421  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
100037689  G6PC1; glucose-6-phosphatase catalytic subunit 1 isoform X1 [KO:K01084] [EC:3.1.3.9]
101121493  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
100037690  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
101120669  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
443434  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
443193  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
101113171  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
101118685  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
101108772  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
101108807  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
101110353  PHKB; phosphorylase b kinase regulatory subunit beta isoform X2 [KO:K07190]
101110737  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
101109323  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
100217403  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
101105840  calmodulin [KO:K02183]
443230  CALM2; calmodulin [KO:K02183]
105614854  calmodulin-alpha [KO:K02183]
101116338  CALM3; calmodulin-3 [KO:K02183]
101115216  CALM1; calmodulin-1 isoform X2 [KO:K02183]
100037684  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
121820456  calmodulin-1-like [KO:K02183]
101123572  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
554320  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
554325  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
442998  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
101116538  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X4 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
100127210  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
101103425  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
101113114  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
101107899  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
100142674  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
101103143  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X3 [KO:K07200]
101104483  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X5 [KO:K07200]
443186  ACACA; acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101114816  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
443461  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
443205  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
101117412  GCK; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
101113198  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
101113460  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
101108592  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
443164  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
443489  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X2 [KO:K00850] [EC:2.7.1.11]
101108532  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
101123502  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
101114294  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
101120366  LOW QUALITY PROTEIN: phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
114108635  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
101103029  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
101110118  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
101113677  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
101121975  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
101118315  L-lactate dehydrogenase C chain isoform X2 [KO:K00016] [EC:1.1.1.27]
443089  LDHA; L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
101118261  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
101107202  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
114118359  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
oas00010  Glycolysis / Gluconeogenesis
oas00020  Citrate cycle (TCA cycle)
oas00061  Fatty acid biosynthesis
oas00190  Oxidative phosphorylation
oas04020  Calcium signaling pathway
oas04024  cAMP signaling pathway
oas04068  FoxO signaling pathway
oas04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

DBGET integrated database retrieval system