KEGG   PATHWAY: ko04917
Entry
ko04917                     Pathway                                

Name
Prolactin signaling pathway
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
ko04917  Prolactin signaling pathway
ko04917

Disease
H01388  Hyperprolactinemia
H01973  Fertile eunuch syndrome
H02019  Familial male-limited precocious puberty
H02061  Estrogen resistance syndrome
Other DBs
GO: 0038161
Orthology
K05439  prolactin
K05081  prolactin receptor
K04447  Janus kinase 2 [EC:2.7.10.2]
K06279  SHC-transforming protein 1
K17447  SHC-transforming protein 2
K17448  SHC-transforming protein 3
K17449  SHC-transforming protein 4
K05704  tyrosine-protein kinase Src [EC:2.7.10.2]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K09408  forkhead box protein O3
K00965  UDPglucose--hexose-1-phosphate uridylyltransferase [EC:2.7.7.12]
K04364  growth factor receptor-binding protein 2
K03099  son of sevenless
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04379  proto-oncogene protein c-fos
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04441  p38 MAP kinase [EC:2.7.11.24]
K04503  G1/S-specific cyclin-D1
K03083  glycogen synthase kinase 3 beta [EC:2.7.11.26]
K04701  cytokine inducible SH2-containing protein
K04694  suppressor of cytokine signaling 1
K04695  suppressor of cytokine signaling 2
K04696  suppressor of cytokine signaling 3
K04697  suppressor of cytokine signaling 4
K04698  suppressor of cytokine signaling 5
K04699  suppressor of cytokine signaling 6/7
K11220  signal transducer and activator of transcription 1
K04692  signal transducer and activator of transcription 3
K11223  signal transducer and activator of transcription 5A
K11224  signal transducer and activator of transcription 5B
K05473  tumor necrosis factor ligand superfamily member 11
K05147  tumor necrosis factor receptor superfamily member 11A
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K17106  whey acidic protein
K17101  E74-like factor 5
K17107  beta-casein
K08522  glycoprotein hormones alpha chain
K08521  lutropin subunit beta
K04248  lutropin-choriogonadotropic hormone receptor
K00512  steroid 17alpha-monooxygenase / 17alpha-hydroxyprogesterone deacetylase [EC:1.14.14.19 1.14.14.32]
K08550  estrogen receptor alpha
K08551  estrogen receptor beta
K09444  interferon regulatory factor 1
K00501  tyrosine 3-monooxygenase [EC:1.14.16.2]
K07593  MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 2
K12407  glucokinase [EC:2.7.1.2]
K10151  G1/S-specific cyclin-D2
K04526  insulin
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
ko04010  MAPK signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04630  JAK-STAT signaling pathway
ko04728  Dopaminergic synapse
ko04911  Insulin secretion
ko04913  Ovarian steroidogenesis
ko04915  Estrogen signaling pathway

DBGET integrated database retrieval system