KEGG   PATHWAY: fca04922
Entry
fca04922                    Pathway                                
Name
Glucagon signaling pathway - Felis catus (domestic cat)
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
fca04922  Glucagon signaling pathway
fca04922

Organism
Felis catus (domestic cat) [GN:fca]
Gene
101087931  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
101094877  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
101097825  GCG; pro-glucagon isoform X2 [KO:K05259]
101099672  GCGR; glucagon receptor [KO:K04583]
101098453  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
102900772  neuroendocrine secretory protein 55 [KO:K04632]
101094327  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
101090494  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X3 [KO:K04345] [EC:2.7.11.11]
101095353  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101090884  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101084297  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101089838  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
101100293  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101100442  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X4 [KO:K09048]
101093555  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101087097  CREB3L1; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101084784  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X7 [KO:K09047]
101093928  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
101095833  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
101081867  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
101101530  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
101101104  CRTC2; CREB-regulated transcription coactivator 2 [KO:K16333]
101091894  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
101088344  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:2.3.1.48]
101094471  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101081802  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X3 [KO:K07202]
101092782  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
101094708  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X2 [KO:K04634]
101090942  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101092961  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101092262  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101090005  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101100546  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101101230  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101087993  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101097144  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101086926  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101093097  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
101097765  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
101090344  PPP3R1; calcineurin subunit B type 1 isoform X4 [KO:K06268]
101098221  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X4 [KO:K04515] [EC:2.7.11.17]
101098090  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
101084342  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101098615  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X2 [KO:K04515] [EC:2.7.11.17]
101096628  FOXO1; forkhead box protein O1 [KO:K07201]
101087610  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
101095837  PPARA; peroxisome proliferator-activated receptor alpha isoform X2 [KO:K07294]
101095389  PRMT1; protein arginine N-methyltransferase 1 isoform X3 [KO:K11434] [EC:2.1.1.319]
101098680  LOW QUALITY PROTEIN: protein arginine N-methyltransferase 1-like [KO:K11434] [EC:2.1.1.319]
723970  G6PC1; glucose-6-phosphatase catalytic subunit 1 [KO:K01084] [EC:3.1.3.9]
101085486  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
101097770  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
101089256  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
101098874  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
101096105  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
101083187  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
101095144  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
101100682  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
101092123  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
101088635  PHKB; phosphorylase b kinase regulatory subunit beta isoform X2 [KO:K07190]
101096789  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
101100185  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
101081184  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
101092572  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
101081534  CALM2; calmodulin-2 [KO:K02183]
101099307  calmodulin-like protein 3 [KO:K02183]
102902667  calmodulin-like [KO:K02183]
101091063  CALM3; calmodulin-3 [KO:K02183]
101097703  calmodulin-alpha-like [KO:K02183]
101094679  CALM1; calmodulin-1 [KO:K02183]
101086824  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
101100214  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
101100836  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
101091099  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
101089364  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
101094910  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
101096000  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
101095885  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X3 [KO:K07198] [EC:2.7.11.31]
101094051  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
101092284  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X3 [KO:K07199]
101094684  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200]
101092204  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X3 [KO:K07200]
101100119  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
101083046  ACACA; acetyl-CoA carboxylase 1 isoform X7 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101086680  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
100127104  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
100142681  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X2 [KO:K07593]
100037406  GCK; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
101084578  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
101084832  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
101088852  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X2 [KO:K00850] [EC:2.7.1.11]
101090792  PFKL; ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
101097072  ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
101094834  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
101099081  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
123378905  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
101080765  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
101081627  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
101100374  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
101092373  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
101100248  LDHA; L-lactate dehydrogenase A chain isoform X2 [KO:K00016] [EC:1.1.1.27]
101086566  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
101100667  LDHC; L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
109492041  LOW QUALITY PROTEIN: L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
101098604  LOW QUALITY PROTEIN: 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
fca00010  Glycolysis / Gluconeogenesis
fca00020  Citrate cycle (TCA cycle)
fca00061  Fatty acid biosynthesis
fca00190  Oxidative phosphorylation
fca04020  Calcium signaling pathway
fca04024  cAMP signaling pathway
fca04068  FoxO signaling pathway
fca04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

DBGET integrated database retrieval system