KEGG   PATHWAY: psiu04922
Entry
psiu04922                   Pathway                                
Name
Glucagon signaling pathway - Phocoena sinus (vaquita)
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
psiu04922  Glucagon signaling pathway
psiu04922

Organism
Phocoena sinus (vaquita) [GN:psiu]
Gene
116743673  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116759669  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116748950  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116758554  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
116756656  GCG; glucagon isoform X1 [KO:K05259]
116745803  GCGR; glucagon receptor [KO:K04583]
116740990  neuroendocrine secretory protein 55-like [KO:K04632]
116740988  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
116752275  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
116754197  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116751566  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
116756730  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
116756632  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
116761029  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
116755320  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
116740243  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
116758621  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
116751955  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
116759300  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
116759616  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
116748364  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
116763478  serine/threonine-protein phosphatase 4 regulatory subunit 3A-like [KO:K17491]
116764114  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
116747024  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
116740627  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
116757632  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
116757414  SIK2; serine/threonine-protein kinase SIK2 isoform X1 [KO:K16311] [EC:2.7.11.1]
116760164  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
116739511  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
116754578  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
116753451  SIK1; serine/threonine-protein kinase SIK1 isoform X1 [KO:K19008] [EC:2.7.11.1]
116755414  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
116749106  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
116740640  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
116740954  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
116758215  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
116761601  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116760890  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
116761675  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116753887  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116755228  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116741444  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116755488  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
116764139  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
116759635  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
116754119  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
116741278  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
116751381  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
116743085  FOXO1; forkhead box protein O1 isoform X1 [KO:K07201]
116741518  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
116760693  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
116744396  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
116746427  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
116739361  glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
116756289  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
116745075  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
116749461  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
116740888  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
116757410  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
116760572  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
116744394  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
116744253  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
116760633  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
116744383  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
116747294  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
116747435  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
116751120  LOW QUALITY PROTEIN: phosphorylase b kinase regulatory subunit beta-like [KO:K07190]
116739983  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
116740362  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
116744236  CALM3; calmodulin-3 [KO:K02183]
116748386  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
116748713  CALM1; calmodulin-1 isoform X1 [KO:K02183]
116762110  calmodulin-1-like [KO:K02183]
116749119  calmodulin-like [KO:K02183]
116749952  calmodulin-like protein 3 [KO:K02183]
116764310  CALM2; calmodulin-2 [KO:K02183]
116749445  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
116740560  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
116757884  PYGM; glycogen phosphorylase, muscle form isoform X1 [KO:K00688] [EC:2.4.1.1]
116748052  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
116739822  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
116751414  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
116741629  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
116765056  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
116760793  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
116756604  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
116759224  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
116746357  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
116765119  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
116750851  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299]
116753535  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
116759611  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
116755412  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
116755592  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
116753372  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
116760160  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
116747794  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
116741512  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
116759338  PGAM2; phosphoglycerate mutase 2 isoform X1 [KO:K01834] [EC:5.4.2.11]
116748496  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
116747360  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
116754568  PDHA2; LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
116761587  PDHB; LOW QUALITY PROTEIN: pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
116743828  LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
116760853  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
116763652  LOW QUALITY PROTEIN: L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
116758350  LOW QUALITY PROTEIN: L-lactate dehydrogenase C chain-like [KO:K00016] [EC:1.1.1.27]
116758623  LDHA; L-lactate dehydrogenase A chain isoform X1 [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
psiu00010  Glycolysis / Gluconeogenesis
psiu00020  Citrate cycle (TCA cycle)
psiu00061  Fatty acid biosynthesis
psiu00190  Oxidative phosphorylation
psiu04020  Calcium signaling pathway
psiu04024  cAMP signaling pathway
psiu04068  FoxO signaling pathway
psiu04910  Insulin signaling pathway
KO pathway
ko04922   
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