KEGG   PATHWAY: cdk04922
Entry
cdk04922                    Pathway                                
Name
Glucagon signaling pathway - Camelus dromedarius (Arabian camel)
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
cdk04922  Glucagon signaling pathway
cdk04922

Organism
Camelus dromedarius (Arabian camel) [GN:cdk]
Gene
105099264  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
105104845  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105093393  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105086706  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B isoform X1 [KO:K13296] [EC:3.1.4.17]
105093688  GCG; glucagon isoform X1 [KO:K05259]
105105706  GCGR; glucagon receptor isoform X1 [KO:K04583]
105095656  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
105095655  neuroendocrine secretory protein 55 [KO:K04632]
105094039  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105095035  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105100776  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105093562  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
105097571  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105091928  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105089327  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
105106926  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105105303  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
105091622  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105102288  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105095833  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105095940  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
105097226  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
105099154  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like [KO:K17491]
105102765  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
105089365  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
105094221  SIK2; LOW QUALITY PROTEIN: serine/threonine-protein kinase SIK2 [KO:K16311] [EC:2.7.11.1]
105091909  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
105099829  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
105098360  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X2 [KO:K07202]
105105909  SIK1; serine/threonine-protein kinase SIK1 isoform X1 [KO:K19008] [EC:2.7.11.1]
105087414  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
105101292  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
105101500  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105101545  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X4 [KO:K05858] [EC:3.1.4.11]
105096910  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105093156  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
105102013  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105101373  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
105102643  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
105092463  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
105089593  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
116152568  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
116157512  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
105089916  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X8 [KO:K04515] [EC:2.7.11.17]
105098484  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
105092453  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
105092345  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
105091004  FOXO1; LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
105093901  SIRT1; LOW QUALITY PROTEIN: NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
105091841  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
105100196  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
105091062  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
105101050  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
105090484  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
105102409  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
105098843  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
105104399  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform isoform X1 [KO:K08765] [EC:2.3.1.21]
105106153  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform [KO:K19523] [EC:2.3.1.21]
105100195  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
105096485  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
105102888  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
105091170  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
105098071  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
105098585  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
105089705  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
105102728  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform [KO:K00871] [EC:2.7.11.19]
105096001  CALM1; calmodulin-1 [KO:K02183]
105093281  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
105104026  CALM3; calmodulin-3 [KO:K02183]
105105602  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
105092364  CALM2; calmodulin-2 [KO:K02183]
116147086  calmodulin-like [KO:K02183]
105101558  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
105091413  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
105099849  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
105103537  PFKFB1; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
105106940  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
105092817  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
105089467  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
105104898  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 isoform X1 [KO:K07199]
105103784  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200]
105098685  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
105096091  PRKAG3; LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
105097853  ACACA; acetyl-CoA carboxylase 1 isoform X1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
105105357  ACACB; acetyl-CoA carboxylase 2 isoform X1 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
105090921  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299]
105086009  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
105092330  GCK; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
105084693  FBP1; fructose-1,6-bisphosphatase 1 isoform X2 [KO:K03841] [EC:3.1.3.11]
105084694  FBP2; fructose-1,6-bisphosphatase isozyme 2 isoform X1 [KO:K03841] [EC:3.1.3.11]
105103995  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
105103800  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
105100510  PFKP; ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
105084280  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
105103438  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
105087293  PKM; pyruvate kinase PKM isoform X2 [KO:K00873] [EC:2.7.1.40]
105089532  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161] [EC:1.2.4.1]
105095309  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
105089807  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
105100946  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
105096484  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
105095329  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
105095330  L-lactate dehydrogenase C 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
cdk00010  Glycolysis / Gluconeogenesis
cdk00020  Citrate cycle (TCA cycle)
cdk00061  Fatty acid biosynthesis
cdk00190  Oxidative phosphorylation
cdk04020  Calcium signaling pathway
cdk04024  cAMP signaling pathway
cdk04068  FoxO signaling pathway
cdk04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

DBGET integrated database retrieval system