KEGG   PATHWAY: mjv04922
Entry
mjv04922                    Pathway                                
Name
Glucagon signaling pathway - Manis javanica (Malayan pangolin)
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
mjv04922  Glucagon signaling pathway
mjv04922

Organism
Manis javanica (Malayan pangolin) [GN:mjv]
Gene
108397433  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108390484  AKT2; RAC-beta serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
108393746  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108396796  PDE3B; cGMP-inhibited 3',5'-cyclic phosphodiesterase B [KO:K13296] [EC:3.1.4.17]
108399525  GCG; pro-glucagon isoform X1 [KO:K05259]
108395230  GCGR; glucagon receptor isoform X10 [KO:K04583]
108406177  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
108406179  neuroendocrine secretory protein 55-like [KO:K04632]
118970338  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
108409724  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
108408343  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
108396160  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
108396432  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
108397369  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
108407563  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
108406808  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048]
108408210  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
108401935  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
108385045  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
108405132  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
108405937  PPP4R3B; serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
108390758  PPP4R3A; serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X2 [KO:K17491]
108396623  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 4 regulatory subunit 3-like [KO:K17491]
108398467  PPP4C; serine/threonine-protein phosphatase 4 catalytic subunit isoform X1 [KO:K15423] [EC:3.1.3.16]
108408207  CRTC2; CREB-regulated transcription coactivator 2 isoform X1 [KO:K16333]
108409552  SIK2; serine/threonine-protein kinase SIK2 isoform X2 [KO:K16311] [EC:2.7.11.1]
108394315  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
108395362  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
108392879  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
108392428  SIK1; serine/threonine-protein kinase SIK1 isoform X2 [KO:K19008] [EC:2.7.11.1]
108397041  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
108407569  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
108394257  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X3 [KO:K05858] [EC:3.1.4.11]
108394259  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
108401653  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
108395952  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
108403293  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
108402938  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
108393196  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
108398753  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
108391436  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
108386668  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
108393727  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
108385398  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
108394027  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
108398760  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
108400883  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
108409638  FOXO1; forkhead box protein O1 [KO:K07201]
108407546  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X2 [KO:K11411] [EC:2.3.1.286]
108406728  PPARA; peroxisome proliferator-activated receptor alpha isoform X1 [KO:K07294]
108400330  PRMT1; protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
108410004  G6PC3; glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
108397568  G6PC2; glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
108394606  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
108390378  PCK2; phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1 [KO:K01596] [EC:4.1.1.32]
108390936  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
108403489  CPT1A; carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
108407876  CPT1B; carnitine O-palmitoyltransferase 1, muscle isoform isoform X2 [KO:K19523] [EC:2.3.1.21]
118970269  carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
108400334  CPT1C; carnitine O-palmitoyltransferase 1, brain isoform isoform X1 [KO:K19524] [EC:2.3.1.21]
108398366  GYS2; glycogen [starch] synthase, liver isoform X1 [KO:K00693] [EC:2.4.1.11]
108400311  GYS1; glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
118970117  glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
108407537  PHKA2; phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
108396139  PHKB; phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
108398608  PHKA1; phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
108405955  PHKG1; phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform [KO:K00871] [EC:2.7.11.19]
108385379  PHKG2; phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
108406654  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
108386142  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
108383704  calmodulin-A-like [KO:K02183]
108406136  CALM3; calmodulin-3 [KO:K02183]
108391461  CALM2; calmodulin-2 [KO:K02183]
108389026  CALM1; calmodulin-1 [KO:K02183]
108402376  PYGL; glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
108396372  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
108396608  PYGB; glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
108384981  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X2 [KO:K07198] [EC:2.7.11.31]
108408223  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
108408200  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
108403327  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199]
108390518  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
108383453  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200]
108405748  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
108384622  ACACA; acetyl-CoA carboxylase 1 [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
108399878  ACACB; acetyl-CoA carboxylase 2 isoform X3 [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
108406715  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
108398018  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
108394025  GCK; hexokinase-4 [KO:K12407] [EC:2.7.1.2]
108393438  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
108393437  FBP2; fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
108403008  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
108403213  PFKL; ATP-dependent 6-phosphofructokinase, liver type isoform X2 [KO:K00850] [EC:2.7.1.11]
108406235  PGAM2; phosphoglycerate mutase 2 isoform X2 [KO:K01834] [EC:5.4.2.11]
108399859  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
108396911  PKM; pyruvate kinase PKM isoform X2 [KO:K00873] [EC:2.7.1.40]
108400925  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
108401242  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
108404130  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
108394911  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial isoform X1 [KO:K00162] [EC:1.2.4.1]
108405097  L-lactate dehydrogenase C chain isoform X1 [KO:K00016] [EC:1.1.1.27]
108405102  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
108398359  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
108395079  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
mjv00010  Glycolysis / Gluconeogenesis
mjv00020  Citrate cycle (TCA cycle)
mjv00061  Fatty acid biosynthesis
mjv00190  Oxidative phosphorylation
mjv04020  Calcium signaling pathway
mjv04024  cAMP signaling pathway
mjv04068  FoxO signaling pathway
mjv04910  Insulin signaling pathway
KO pathway
ko04922   
LinkDB

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