KEGG   PATHWAY: hsa04917
Entry
hsa04917                    Pathway                                

Name
Prolactin signaling pathway - Homo sapiens (human)
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
hsa04917  Prolactin signaling pathway
hsa04917

Network
nt06325  PRL signaling
  Element
N00920  PRL-JAK-STAT signaling pathway
N00921  Mutation-inactivated PRLR to PRL-JAK-STAT signaling pathway
Disease
H01388  Hyperprolactinemia
H01973  Fertile eunuch syndrome
H02019  Familial male-limited precocious puberty
H02061  Estrogen resistance syndrome
Drug
D00780  Bromocriptine mesylate (USP)
D00987  Cabergoline (JAN/USP/INN)
D01348  Terguride (JAN/INN)
D03165  Bromocriptine (USAN/INN)
D06631  Prinaberel (USAN/INN)
Other DBs
GO: 0038161
Organism
Homo sapiens (human) [GN:hsa]
Gene
5617  PRL; prolactin [KO:K05439]
5618  PRLR; prolactin receptor [KO:K05081]
3717  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
6464  SHC1; SHC adaptor protein 1 [KO:K06279]
25759  SHC2; SHC adaptor protein 2 [KO:K17447]
53358  SHC3; SHC adaptor protein 3 [KO:K17448]
399694  SHC4; SHC adaptor protein 4 [KO:K17449]
6714  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
2309  FOXO3; forkhead box O3 [KO:K09408]
2592  GALT; galactose-1-phosphate uridylyltransferase [KO:K00965] [EC:2.7.7.12]
2885  GRB2; growth factor receptor bound protein 2 [KO:K04364]
6654  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
2353  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
595  CCND1; cyclin D1 [KO:K04503]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
1154  CISH; cytokine inducible SH2 containing protein [KO:K04701]
8651  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
8835  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
9021  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
122809  SOCS4; suppressor of cytokine signaling 4 [KO:K04697]
9655  SOCS5; suppressor of cytokine signaling 5 [KO:K04698]
30837  SOCS7; suppressor of cytokine signaling 7 [KO:K04699]
9306  SOCS6; suppressor of cytokine signaling 6 [KO:K04699]
6772  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
6774  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
6776  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
6777  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
8600  TNFSF11; TNF superfamily member 11 [KO:K05473]
8792  TNFRSF11A; TNF receptor superfamily member 11a [KO:K05147]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
2001  ELF5; E74 like ETS transcription factor 5 [KO:K17101]
1447  CSN2; casein beta [KO:K17107]
1081  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
3972  LHB; luteinizing hormone subunit beta [KO:K08521]
3973  LHCGR; luteinizing hormone/choriogonadotropin receptor [KO:K04248]
1586  CYP17A1; cytochrome P450 family 17 subfamily A member 1 [KO:K00512] [EC:1.14.14.19 1.14.14.32]
2099  ESR1; estrogen receptor 1 [KO:K08550]
2100  ESR2; estrogen receptor 2 [KO:K08551]
3659  IRF1; interferon regulatory factor 1 [KO:K09444]
7054  TH; tyrosine hydroxylase [KO:K00501] [EC:1.14.16.2]
6514  SLC2A2; solute carrier family 2 member 2 [KO:K07593]
2645  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
894  CCND2; cyclin D2 [KO:K10151]
3630  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
hsa04010  MAPK signaling pathway
hsa04151  PI3K-Akt signaling pathway
hsa04630  JAK-STAT signaling pathway
hsa04728  Dopaminergic synapse
hsa04911  Insulin secretion
hsa04913  Ovarian steroidogenesis
hsa04915  Estrogen signaling pathway
KO pathway
ko04917   

  All links  
Network (2)   
   KEGG NETWORK (2)   
Disease (4)   
   KEGG DISEASE (4)   
Genome (1)   
   KEGG GENOME (1)   
Gene (70)   
   KEGG GENES (70)   
All databases (77)   

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