KEGG   PATHWAY: sara04922
Entry
sara04922                   Pathway                                
Name
Glucagon signaling pathway - Sorex araneus (European shrew)
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
sara04922  Glucagon signaling pathway
sara04922

Organism
Sorex araneus (European shrew) [GN:sara]
Gene
101543096  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101559009  AKT2; RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101543371  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101554408  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
101537193  GCG; glucagon [KO:K05259]
101550812  GCGR; glucagon receptor [KO:K04583]
101539470  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
101539413  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101539926  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101555578  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
101546696  cAMP-dependent protein kinase catalytic subunit-like [KO:K04345] [EC:2.7.11.11]
101554719  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
101552417  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101539734  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101539159  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101554214  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101538215  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
101543170  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101542980  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101553377  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
101554016  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
101537025  SMEK2; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
101555014  SMEK1; serine/threonine-protein phosphatase 4 regulatory subunit 3A [KO:K17491]
101537493  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
101548618  CRTC2; CREB-regulated transcription coactivator 2 [KO:K16333]
101558225  SIK2; serine/threonine-protein kinase SIK2 [KO:K16311] [EC:2.7.11.1]
101542504  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101558222  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
101537912  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
101541844  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
101557809  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101551223  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101546811  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101547690  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101559179  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101556467  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101556630  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101555935  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101557366  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101558512  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
101555223  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
101556800  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
101541742  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
101545625  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101542258  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
101549665  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101549827  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
101557018  FOXO1; forkhead box protein O1 [KO:K07201]
101541735  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
101551757  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
101547192  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
101538185  G6PC; glucose-6-phosphatase [KO:K01084] [EC:3.1.3.9]
101542369  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
101552141  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
101538679  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
101544421  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
101556388  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
101547962  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
101543436  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
101541824  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
101537735  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
101556499  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform [KO:K07190]
101553733  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
101541620  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
101553368  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
101543506  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
101554401  CALM1; calmodulin isoform X1 [KO:K02183]
101552535  CALML3; calmodulin-like protein 3 [KO:K02183]
101545302  CALML5; calmodulin-like protein 5 [KO:K02183]
101546941  CALML4; calmodulin-like protein 4 [KO:K02183]
101541555  CALM2; calmodulin [KO:K02183]
101543973  calmodulin-like [KO:K02183]
101559307  CALM3; calmodulin [KO:K02183]
101552224  PYGM; glycogen phosphorylase, muscle form isoform X1 [KO:K00688] [EC:2.4.1.1]
101558560  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
101551797  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
101542481  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
101550327  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
101541971  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
101551786  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
101537509  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
101556652  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
101541203  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
101550416  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101546832  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101542959  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
101557379  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
101537755  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
101553579  LOW QUALITY PROTEIN: fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
101557935  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
101537732  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
101544635  PFKP; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
101539745  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
101550265  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
101557516  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
101539691  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
101542247  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
101557550  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
101537121  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
105942796  L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
101547049  LDHA; L-lactate dehydrogenase A chain isoform X1 [KO:K00016] [EC:1.1.1.27]
101547494  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
sara00010  Glycolysis / Gluconeogenesis
sara00020  Citrate cycle (TCA cycle)
sara00061  Fatty acid biosynthesis
sara00190  Oxidative phosphorylation
sara04020  Calcium signaling pathway
sara04024  cAMP signaling pathway
sara04068  FoxO signaling pathway
sara04910  Insulin signaling pathway
KO pathway
ko04922   
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