KEGG   PATHWAY: sbq04922
Entry
sbq04922                    Pathway                                
Name
Glucagon signaling pathway - Saimiri boliviensis boliviensis (Bolivian squirrel monkey)
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
sbq04922  Glucagon signaling pathway
sbq04922

Organism
Saimiri boliviensis boliviensis (Bolivian squirrel monkey) [GN:sbq]
Gene
101034861  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101045714  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101040766  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101046670  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
101041383  GCG; glucagon [KO:K05259]
101035800  GCGR; glucagon receptor isoform X1 [KO:K04583]
101043452  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
104652116  neuroendocrine secretory protein 55 [KO:K04632]
101043334  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101034152  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
101036705  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
101043989  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]
101047300  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101034085  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101035834  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101034435  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101042795  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101044974  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101036473  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
101052885  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101041199  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X4 [KO:K09048]
101054090  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
101035428  putative SMEK homolog 3 [KO:K17491]
101045837  SMEK1; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
101038598  SMEK2; serine/threonine-protein phosphatase 4 regulatory subunit 3B [KO:K17491]
101037597  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
101040859  CRTC2; CREB-regulated transcription coactivator 2 isoform X2 [KO:K16333]
101032802  SIK2; serine/threonine-protein kinase SIK2 [KO:K16311] [EC:2.7.11.1]
101033803  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101050224  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101046514  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X2 [KO:K07202]
101032736  SIK1; serine/threonine-protein kinase SIK1 [KO:K19008] [EC:2.7.11.1]
101051855  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101046851  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
101047168  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
101052271  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101029401  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101029556  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101049881  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101048916  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101045514  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
101035788  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101032266  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101039659  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
104650539  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
101031635  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
101041452  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101052251  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
101041781  LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II delta chain-like [KO:K04515] [EC:2.7.11.17]
101038342  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X10 [KO:K04515] [EC:2.7.11.17]
101053657  FOXO1; forkhead box protein O1 [KO:K07201]
101029573  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
101032215  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
101033444  PRMT1; protein arginine N-methyltransferase 1 isoform X2 [KO:K11434] [EC:2.1.1.319]
101036723  G6PC3; glucose-6-phosphatase 3 [KO:K01084] [EC:3.1.3.9]
101033884  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
101032250  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
101027719  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
101035593  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X2 [KO:K01596] [EC:4.1.1.32]
101044692  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
101045068  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
101043828  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
101040983  GYS2; glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
101050509  GYS1; glycogen [starch] synthase, muscle isoform X1 [KO:K00693] [EC:2.4.1.11]
101039573  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X2 [KO:K07190]
101052401  PHKB; phosphorylase b kinase regulatory subunit beta isoform X2 [KO:K07190]
101054139  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X2 [KO:K07190]
101045885  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
101048522  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
101036413  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
101031785  calmodulin-alpha-like [KO:K02183]
101041174  CALML6; calmodulin-like protein 6 isoform X2 [KO:K02183]
101029957  CALM3; calmodulin [KO:K02183]
101047982  CALM2; calmodulin [KO:K02183]
101039332  CALML3; calmodulin-like protein 3 [KO:K02183]
101039863  CALML5; calmodulin-like protein 5 [KO:K02183]
101049022  CALM1; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
101044400  PYGL; glycogen phosphorylase, liver form [KO:K00688] [EC:2.4.1.1]
101032178  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
101053900  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
101034307  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
101030830  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X2 [KO:K07198] [EC:2.7.11.31]
101033212  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
101029046  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
101051388  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
101028682  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200]
101044457  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
101042380  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
101031989  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101037726  ACACB; acetyl-CoA carboxylase 2 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
101049410  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
101053596  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
101027980  GCK; glucokinase isoform X1 [KO:K12407] [EC:2.7.1.2]
101028234  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
101028557  FBP1; fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
101031244  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
101044335  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
101040210  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
101053434  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
101028879  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
104651218  phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
101027444  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
101051150  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
101046119  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
101028429  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
101041318  LDHB; LOW QUALITY PROTEIN: L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
101029986  LOW QUALITY PROTEIN: L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
101045050  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
101047497  LOW QUALITY PROTEIN: L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
101047174  L-lactate dehydrogenase C chain isoform X1 [KO:K00016] [EC:1.1.1.27]
101048261  LDHAL6A; 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
sbq00010  Glycolysis / Gluconeogenesis
sbq00020  Citrate cycle (TCA cycle)
sbq00061  Fatty acid biosynthesis
sbq00190  Oxidative phosphorylation
sbq04020  Calcium signaling pathway
sbq04024  cAMP signaling pathway
sbq04068  FoxO signaling pathway
sbq04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

DBGET integrated database retrieval system