KEGG   PATHWAY: afz04922
Entry
afz04922                    Pathway                                
Name
Glucagon signaling pathway - Antechinus flavipes (yellow-footed antechinus)
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
afz04922  Glucagon signaling pathway
afz04922

Organism
Antechinus flavipes (yellow-footed antechinus) [GN:afz]
Gene
127549861  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127556193  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
127559596  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
127542140  cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B isoform X1 [KO:K13296] [EC:3.1.4.17]
127554614  pro-glucagon isoform X1 [KO:K05259]
127560637  glucagon receptor [KO:K04583]
127548965  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
127543614  adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
127548938  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
127563015  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
127543087  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
127544835  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
127553178  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
127554549  cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
127538329  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
127538146  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
127544947  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
127559872  cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
127539809  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
127540403  cyclic AMP-responsive element-binding protein 3 [KO:K09048]
127539046  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
127549404  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
127548096  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 4 regulatory subunit 3B [KO:K17491]
127556105  serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
127559878  CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
127554974  serine/threonine-protein kinase SIK2 [KO:K16311] [EC:2.7.11.1]
127542170  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
127538400  histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
127539643  peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
127553798  serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
127541331  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
127549225  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
127539641  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
127548499  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
127548500  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
127551451  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
127539174  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
127561144  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
127551919  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127548327  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127540919  protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
127548157  calcineurin subunit B type 1 isoform X1 [KO:K06268]
127548830  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
127550086  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
127551909  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
127540938  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
127555224  forkhead box protein O1 [KO:K07201]
127552112  NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
127538966  peroxisome proliferator-activated receptor alpha [KO:K07294]
127556563  protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
127558014  LOW QUALITY PROTEIN: glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
127560091  glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
127560332  glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
127548953  phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
127551073  phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
127540255  carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
127538809  carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
127556546  carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
127564537  glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
127556548  glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
127542818  phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
127550680  phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
127553591  phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
127562946  phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
127558725  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
127564795  calmodulin-A-like [KO:K02183]
127549410  calmodulin-1 [KO:K02183]
127555994  calmodulin-like protein 6 [KO:K02183]
127556283  calmodulin-3 [KO:K02183]
127551228  calmodulin-like protein 4 isoform X1 [KO:K02183]
127548058  calmodulin-2 [KO:K02183]
127549785  glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
127540082  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
127548413  glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
127543201  6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
127563258  5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
127556825  5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
127545541  LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
127559188  5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
127564149  5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
127538054  5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
127553096  5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
127559918  acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
127545590  acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
127555557  solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
127552868  solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
127548834  hexokinase-4 [KO:K12407] [EC:2.7.1.2]
127544019  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
127548047  fructose-1,6-bisphosphatase 1-like [KO:K03841] [EC:3.1.3.11]
127561719  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
127561726  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
127562454  ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
127537829  ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
127538403  ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
127551749  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
127551836  pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
127562789  pyruvate dehydrogenase E1 component subunit alpha, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
127553984  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
127550698  pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
127564229  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
127538096  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
127539849  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
127540293  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
127540665  L-lactate dehydrogenase A 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
afz00010  Glycolysis / Gluconeogenesis
afz00020  Citrate cycle (TCA cycle)
afz00061  Fatty acid biosynthesis
afz00190  Oxidative phosphorylation
afz04020  Calcium signaling pathway
afz04024  cAMP signaling pathway
afz04068  FoxO signaling pathway
afz04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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