KEGG   PATHWAY: ngi04917
Entry
ngi04917                    Pathway                                
Name
Prolactin signaling pathway - Nannospalax galili (Upper Galilee mountains blind mole rat)
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
ngi04917  Prolactin signaling pathway
ngi04917

Other DBs
GO: 0038161
Organism
Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]
Gene
103739991  prolactin-like [KO:K05439]
103739983  prolactin-like [KO:K05439]
108491197  prolactin-like [KO:K05439]
103739985  prolactin-7B1-like [KO:K05439]
103739984  prolactin-7C1-like [KO:K05439]
108491199  prolactin-3B1-like [KO:K05439]
103739988  prolactin-7B1-like [KO:K05439]
108491200  prolactin-3D4-like [KO:K05439]
103739987  prolactin-7C1-like [KO:K05439]
103751156  prolactin-3B1-like [KO:K05439]
108490016  prolactin-3B1-like [KO:K05439]
103751328  prolactin [KO:K05439]
103728738  prolactin-like [KO:K05439]
103728740  prolactin-5A1-like [KO:K05439]
103728741  prolactin-5A1-like [KO:K05439]
103728734  prolactin-2A1-like [KO:K05439]
103728735  prolactin-like [KO:K05439]
103728739  prolactin-2A1-like [KO:K05439]
103735901  Prlr; prolactin receptor [KO:K05081]
103740979  Jak2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
103751254  Shc1; SHC adaptor protein 1 [KO:K06279]
103737407  Shc2; SHC adaptor protein 2 [KO:K17447]
103726215  Shc3; SHC adaptor protein 3 [KO:K17448]
103733036  Shc4; SHC adaptor protein 4 [KO:K17449]
103752029  Src; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
103738596  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103733121  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103742946  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103738715  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103726879  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103730305  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103746884  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103750757  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103752536  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103749566  Foxo3; forkhead box O3 [KO:K09408]
103741563  Galt; galactose-1-phosphate uridylyltransferase [KO:K00965] [EC:2.7.7.12]
103732729  Grb2; growth factor receptor bound protein 2 [KO:K04364]
103743944  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103731514  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103751075  Hras; HRas proto-oncogene, GTPase [KO:K02833]
103736717  Kras; KRAS proto-oncogene, GTPase [KO:K07827]
103734938  Nras; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103751450  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103736801  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103737276  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103741442  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103726390  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103747342  Fos; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
103735023  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103748972  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103749366  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103739660  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103739659  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103735473  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103735474  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103751498  Ccnd1; cyclin D1 [KO:K04503]
103741948  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103750144  Cish; cytokine inducible SH2 containing protein [KO:K04701]
103731577  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
103726290  Socs2; suppressor of cytokine signaling 2 [KO:K04695]
103747288  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
103739222  Socs4; suppressor of cytokine signaling 4 [KO:K04697]
103725749  Socs5; suppressor of cytokine signaling 5 [KO:K04698]
103743791  Socs7; suppressor of cytokine signaling 7 [KO:K04699]
103727130  Socs6; suppressor of cytokine signaling 6 [KO:K04699]
103736156  Stat1; signal transducer and activator of transcription 1 [KO:K11220]
103735896  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
103735895  Stat5a; signal transducer and activator of transcription 5A [KO:K11223]
103735893  Stat5b; signal transducer and activator of transcription 5B [KO:K11224]
103751291  Tnfsf11; tumor necrosis factor superfamily member 11 [KO:K05473]
103740116  Tnfrsf11a; TNF receptor superfamily member 11a [KO:K05147]
103728077  Nfkb1; nuclear factor kappa B subunit 1 [KO:K02580]
103724994  Rela; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103735002  whey acidic protein-like [KO:K17106]
103749496  Elf5; E74 like ETS transcription factor 5 [KO:K17101]
103731256  Csn2; casein beta [KO:K17107]
103729473  Cga; glycoprotein hormones, alpha polypeptide [KO:K08522]
103743644  Lhb; luteinizing hormone beta polypeptide [KO:K08521]
103725730  Lhcgr; luteinizing hormone/choriogonadotropin receptor [KO:K04248]
103744072  steroid 17-alpha-hydroxylase/17,20 lyase [KO:K00512] [EC:1.14.14.19 1.14.14.32]
103745757  Esr1; estrogen receptor 1 [KO:K08550]
103747954  Esr2; estrogen receptor 2 [KO:K08551]
103747025  Irf1; interferon regulatory factor 1 [KO:K09444]
103738985  Th; tyrosine hydroxylase [KO:K00501] [EC:1.14.16.2]
103731696  Slc2a2; solute carrier family 2 member 2 [KO:K07593]
103734982  Gck; glucokinase [KO:K12407] [EC:2.7.1.2]
103727547  Ccnd2; cyclin D2 [KO:K10151]
103738986  Ins; insulin [KO:K04526]
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
ngi04010  MAPK signaling pathway
ngi04151  PI3K-Akt signaling pathway
ngi04630  JAK-STAT signaling pathway
ngi04728  Dopaminergic synapse
ngi04911  Insulin secretion
ngi04913  Ovarian steroidogenesis
ngi04915  Estrogen signaling pathway
KO pathway
ko04917   
LinkDB

DBGET integrated database retrieval system