KEGG   PATHWAY: lruf04922
Entry
lruf04922                   Pathway                                
Name
Glucagon signaling pathway - Lynx rufus (bobcat)
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
lruf04922  Glucagon signaling pathway
lruf04922

Organism
Lynx rufus (bobcat) [GN:lruf]
Gene
124510270  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
124511119  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124512474  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124504956  cGMP-inhibited 3',5'-cyclic phosphodiesterase B-like [KO:K13296] [EC:3.1.4.17]
124514442  pro-glucagon [KO:K05259]
124522597  glucagon receptor-like [KO:K04583]
124503012  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
124503255  neuroendocrine secretory protein 55 [KO:K04632]
124508049  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
124514583  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
124524048  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
124516566  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
124514138  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
124502100  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
124524408  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
124506275  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
124521809  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
124501745  cyclic AMP-responsive element-binding protein 3-like isoform X1 [KO:K09048]
124523866  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
124524308  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
124503641  serine/threonine-protein phosphatase 4 regulatory subunit 3B isoform X1 [KO:K17491]
124512572  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1 [KO:K17491]
124509662  serine/threonine-protein phosphatase 4 regulatory subunit 3B-like isoform X1 [KO:K17491]
124517738  serine/threonine-protein phosphatase 4 catalytic subunit [KO:K15423] [EC:3.1.3.16]
124521777  CREB-regulated transcription coactivator 2 [KO:K16333]
124504616  serine/threonine-protein kinase SIK2 [KO:K16311] [EC:2.7.11.1]
124517735  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
124501617  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
124520204  peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202]
124526566  serine/threonine-protein kinase SIK1-like [KO:K19008] [EC:2.7.11.1]
124528694  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
124503791  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4-like [KO:K05858] [EC:3.1.4.11]
124503878  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
124505119  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
124508712  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
124522957  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
124501326  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
124528059  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
124519949  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
124521006  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
124506908  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
124504103  calcineurin subunit B type 1 [KO:K06268]
124502506  calcineurin subunit B type 2 [KO:K06268]
124524655  calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
124520612  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
124506916  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
124521364  calcium/calmodulin-dependent protein kinase type II subunit alpha-like [KO:K04515] [EC:2.7.11.17]
124511738  forkhead box protein O1 [KO:K07201]
124506847  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
124502565  peroxisome proliferator-activated receptor alpha [KO:K07294]
124510898  protein arginine N-methyltransferase 1 isoform X1 [KO:K11434] [EC:2.1.1.319]
124514520  glucose-6-phosphatase 2 [KO:K01084] [EC:3.1.3.9]
124522084  glucose-6-phosphatase 3 isoform X1 [KO:K01084] [EC:3.1.3.9]
124522255  glucose-6-phosphatase catalytic subunit 1 isoform X1 [KO:K01084] [EC:3.1.3.9]
124504096  phosphoenolpyruvate carboxykinase, cytosolic [GTP] [KO:K01596] [EC:4.1.1.32]
124508838  phosphoenolpyruvate carboxykinase [GTP], mitochondrial [KO:K01596] [EC:4.1.1.32]
124504618  carnitine O-palmitoyltransferase 1, liver isoform [KO:K08765] [EC:2.3.1.21]
124502379  carnitine O-palmitoyltransferase 1, muscle isoform isoform X1 [KO:K19523] [EC:2.3.1.21]
124510897  carnitine O-palmitoyltransferase 1, brain isoform [KO:K19524] [EC:2.3.1.21]
124510925  glycogen [starch] synthase, muscle [KO:K00693] [EC:2.4.1.11]
124502618  glycogen [starch] synthase, liver [KO:K00693] [EC:2.4.1.11]
124511289  phosphorylase b kinase regulatory subunit beta isoform X1 [KO:K07190]
124521567  phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform isoform X1 [KO:K07190]
124509396  phosphorylase b kinase regulatory subunit alpha, liver isoform isoform X1 [KO:K07190]
124518077  phosphorylase b kinase gamma catalytic chain, liver/testis isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
124519328  phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform isoform X1 [KO:K00871] [EC:2.7.11.19]
124503379  calmodulin-1 [KO:K02183]
124510996  calmodulin-1 [KO:K02183]
124512578  calmodulin-1 [KO:K02183]
124514424  LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
124508455  LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
124502502  calmodulin-like protein 3 [KO:K02183]
124502628  calmodulin-like [KO:K02183]
124504873  glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
124512201  glycogen phosphorylase, liver form isoform X1 [KO:K00688] [EC:2.4.1.1]
124503091  glycogen phosphorylase, brain form [KO:K00688] [EC:2.4.1.1]
124522295  6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1 isoform X1 [KO:K19028] [EC:2.7.1.105 3.1.3.46]
124521983  5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
124515130  5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
124518202  5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
124515471  5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
124501542  5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
124515810  5'-AMP-activated protein kinase subunit gamma-3-like isoform X1 [KO:K07200]
124522961  5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
124513125  acetyl-CoA carboxylase 1-like [KO:K11262] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
124518440  LOW QUALITY PROTEIN: acetyl-CoA carboxylase 2-like [KO:K01946] [EC:6.4.1.2 6.3.4.14 2.1.3.15]
124515644  solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
124526881  solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
124524269  hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
124525433  fructose-1,6-bisphosphatase isozyme 2 [KO:K03841] [EC:3.1.3.11]
124525442  fructose-1,6-bisphosphatase 1 [KO:K03841] [EC:3.1.3.11]
124526236  ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
124501338  ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
124502465  ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
124507030  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
124523676  phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
124508427  pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
124521338  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like isoform X1 [KO:K00161] [EC:1.2.4.1]
124509400  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
124513865  pyruvate dehydrogenase E1 component subunit beta, mitochondrial-like [KO:K00162] [EC:1.2.4.1]
124522839  pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
124505110  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
124505180  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
124506216  L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
124528295  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
124507753  LOW QUALITY PROTEIN: L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
124529375  L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
124502309  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
124509583  L-lactate dehydrogenase A chain-like [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
lruf00010  Glycolysis / Gluconeogenesis
lruf00020  Citrate cycle (TCA cycle)
lruf00061  Fatty acid biosynthesis
lruf00190  Oxidative phosphorylation
lruf04020  Calcium signaling pathway
lruf04024  cAMP signaling pathway
lruf04068  FoxO signaling pathway
lruf04910  Insulin signaling pathway
KO pathway
ko04922   
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