KEGG   PATHWAY: epz04917
Entry
epz04917                    Pathway                                
Name
Prolactin signaling pathway - Equus przewalskii (Przewalski's horse)
Description
Prolactin (PRL) is a polypeptide hormone known to be involved in a wide range of biological functions including osmoregulation, lactation, reproduction, growth and development, endocrinology and metabolism, brain and behavior, and immunomodulation. PRL mediates its action through PRLR, a transmembrane protein of the hematopoietin cytokine receptor superfamily. At the protein level, the long PRLR isoform (long-R) and several short PRLR isoforms (short-R) have been detected. Acting through the long-R, PRL activates many signaling cascades including Jak2/Stat, the major cascade, Src kinase, phosphatidylinositol-3-kinase (PI3K)/AKT, and mitogen-activated protein kinase (MAPK) pathways. PRL cannot activate Jak2/Stat5 through the short-R, but can activate pathways including MAPK and PI3K pathways.
Class
Organismal Systems; Endocrine system
Pathway map
epz04917  Prolactin signaling pathway
epz04917

Other DBs
GO: 0038161
Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103540089  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
103540249  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103542441  SHC2; SHC-transforming protein 2 [KO:K17447]
103542876  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103543290  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103543692  RELA; transcription factor p65 [KO:K04735]
103545339  PRLR; prolactin receptor [KO:K05081]
103545553  TH; tyrosine 3-monooxygenase isoform X1 [KO:K00501] [EC:1.14.16.2]
103546363  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
103546580  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103546629  KRAS; GTPase KRas isoform X1 [KO:K07827]
103547261  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103547424  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103547564  ESR1; estrogen receptor isoform X1 [KO:K08550]
103547763  CGA; glycoprotein hormones alpha chain [KO:K08522]
103548220  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
103548618  FOS; protein c-Fos [KO:K04379]
103548655  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
103549076  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103549414  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103549630  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
103550364  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
103550390  [KO:K11223]
103550391  [KO:K11224]
103550588  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103551216  FOXO3; forkhead box protein O3 isoform X3 [KO:K09408]
103551857  SHC4; SHC-transforming protein 4 [KO:K17449]
103551868  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
103552150  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103552516  SHC3; SHC-transforming protein 3 [KO:K17448]
103552675  NRAS; GTPase NRas [KO:K07828]
103552865  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
103553088  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
103553307  [KO:K08521]
103553980  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103554055  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
103554102  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
103554269  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
103554330  ESR2; estrogen receptor beta [KO:K08551]
103554541  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103554943  GCK; hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
103555098  PRL; prolactin isoform X2 [KO:K05439]
103555421  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103556123  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103556719  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103556909  LHCGR; lutropin-choriogonadotropic hormone receptor isoform X1 [KO:K04248]
103558137  CYP17A1; steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
103558714  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
103559273  CISH; cytokine-inducible SH2-containing protein isoform X1 [KO:K04701]
103559485  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103559491  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
103559705  SOCS7; suppressor of cytokine signaling 7 isoform X1 [KO:K04699]
103560371  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
103560497  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103560907  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
103561476  ELF5; ETS-related transcription factor Elf-5 isoform X4 [KO:K17101]
103561550  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
103562408  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103562575  TNFRSF11A; tumor necrosis factor receptor superfamily member 11A isoform X1 [KO:K05147]
103563198  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
103563209  IRF1; interferon regulatory factor 1 [KO:K09444]
103564583  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
103565534  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103565620  CSN2; beta-casein isoform X3 [KO:K17107]
103567332  HRAS; GTPase HRas isoform X1 [KO:K02833]
103567614  INS; insulin [KO:K04526]
103567629  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103567717  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
139074765  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
139085032  [KO:K07827]
Compound
C00002  ATP
C00031  D-Glucose
C00082  L-Tyrosine
C00092  D-Glucose 6-phosphate
C00280  Androstenedione
C00355  3,4-Dihydroxy-L-phenylalanine
C00410  Progesterone
C00468  Estrone
C00951  Estradiol-17beta
C03758  Dopamine
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Binart N, Bachelot A, Bouilly J
  Title
Impact of prolactin receptor isoforms on reproduction.
  Journal
Trends Endocrinol Metab 21:362-8 (2010)
DOI:10.1016/j.tem.2010.01.008
Reference
  Authors
Bachelot A, Binart N
  Title
Reproductive role of prolactin.
  Journal
Reproduction 133:361-9 (2007)
DOI:10.1530/REP-06-0299
Reference
  Authors
Hennighausen L, Robinson GW
  Title
Information networks in the mammary gland.
  Journal
Nat Rev Mol Cell Biol 6:715-25 (2005)
DOI:10.1038/nrm1714
Reference
  Authors
Bouilly J, Sonigo C, Auffret J, Gibori G, Binart N
  Title
Prolactin signaling mechanisms in ovary.
  Journal
Mol Cell Endocrinol 356:80-7 (2012)
DOI:10.1016/j.mce.2011.05.004
Reference
  Authors
Oakes SR, Rogers RL, Naylor MJ, Ormandy CJ
  Title
Prolactin regulation of mammary gland development.
  Journal
J Mammary Gland Biol Neoplasia 13:13-28 (2008)
DOI:10.1007/s10911-008-9069-5
Reference
  Authors
Frasor J, Gibori G
  Title
Prolactin regulation of estrogen receptor expression.
  Journal
Trends Endocrinol Metab 14:118-23 (2003)
DOI:10.1016/S1043-2760(03)00030-4
Reference
PMID:9626554
  Authors
Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA
  Title
Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice.
  Journal
Endocr Rev 19:225-68 (1998)
DOI:10.1210/edrv.19.3.0334
Reference
  Authors
Weinhaus AJ, Stout LE, Bhagroo NV, Brelje TC, Sorenson RL
  Title
Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for increasing glucose-stimulated insulin secretion during pregnancy.
  Journal
J Endocrinol 193:367-81 (2007)
DOI:10.1677/JOE-07-0043
Reference
  Authors
Grattan DR, Kokay IC
  Title
Prolactin: a pleiotropic neuroendocrine hormone.
  Journal
J Neuroendocrinol 20:752-63 (2008)
DOI:10.1111/j.1365-2826.2008.01736.x
Reference
PMID:9475379
  Authors
Yu-Lee LY, Luo G, Book ML, Morris SM
  Title
Lactogenic hormone signal transduction.
  Journal
Biol Reprod 58:295-301 (1998)
DOI:10.1095/biolreprod58.2.295
Reference
  Authors
Tam SP, Lau P, Djiane J, Hilton DJ, Waters MJ
  Title
Tissue-specific induction of SOCS gene expression by PRL.
  Journal
Endocrinology 142:5015-26 (2001)
DOI:10.1210/endo.142.11.8466
Reference
  Authors
Halperin J, Devi SY, Elizur S, Stocco C, Shehu A, Rebourcet D, Unterman TG, Leslie ND, Le J, Binart N, Gibori G
  Title
Prolactin signaling through the short form of its receptor represses forkhead transcription factor FOXO3 and its target gene galt causing a severe ovarian defect.
  Journal
Mol Endocrinol 22:513-22 (2008)
DOI:10.1210/me.2007-0399
Reference
  Authors
Sakamoto K, Creamer BA, Triplett AA, Wagner KU
  Title
The Janus kinase 2 is required for expression and nuclear accumulation of cyclin D1 in proliferating mammary epithelial cells.
  Journal
Mol Endocrinol 21:1877-92 (2007)
DOI:10.1210/me.2006-0316
Reference
  Authors
Oakes SR, Hilton HN, Ormandy CJ
  Title
The alveolar switch: coordinating the proliferative cues and cell fate decisions that drive the formation of lobuloalveoli from ductal epithelium.
  Journal
Breast Cancer Res 8:207 (2006)
DOI:10.1186/bcr1411
Related
pathway
epz04010  MAPK signaling pathway
epz04151  PI3K-Akt signaling pathway
epz04630  JAK-STAT signaling pathway
epz04728  Dopaminergic synapse
epz04911  Insulin secretion
epz04913  Ovarian steroidogenesis
epz04915  Estrogen signaling pathway
KO pathway
ko04917   

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