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

Other DBs
GO: 0038161
Orthology
K00501  TH; tyrosine 3-monooxygenase [EC:1.14.16.2]
K00512  CYP17A; steroid 17alpha-monooxygenase / 17alpha-hydroxyprogesterone deacetylase [EC:1.14.14.19 1.14.14.32]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K00965  galT; UDPglucose--hexose-1-phosphate uridylyltransferase [EC:2.7.7.12]
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02833  HRAS; GTPase HRas
K03083  GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]
K03099  SOS; son of sevenless
K04248  LHCGR; lutropin-choriogonadotropic hormone receptor
K04364  GRB2; growth factor receptor-bound protein 2
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04379  FOS; proto-oncogene protein c-fos
K04440  JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04441  P38; p38 MAP kinase [EC:2.7.11.24]
K04447  JAK2; Janus kinase 2 [EC:2.7.10.2]
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04503  CCND1; G1/S-specific cyclin-D1
K04526  INS; insulin
K04692  STAT3; signal transducer and activator of transcription 3
K04694  SOCS1, JAB; suppressor of cytokine signaling 1
K04695  SOCS2, CIS2; suppressor of cytokine signaling 2
K04696  SOCS3, CIS3; suppressor of cytokine signaling 3
K04697  SOCS4; suppressor of cytokine signaling 4
K04698  SOCS5; suppressor of cytokine signaling 5
K04699  SOCS6_7; suppressor of cytokine signaling 6/7
K04701  CISH; cytokine inducible SH2-containing protein
K04735  RELA; transcription factor p65
K05081  PRLR; prolactin receptor
K05147  TNFRSF11A, RANK, CD265; tumor necrosis factor receptor superfamily member 11A
K05439  PRL; prolactin
K05473  TNFSF11, RANKL, CD254; tumor necrosis factor ligand superfamily member 11
K05704  SRC; tyrosine-protein kinase Src [EC:2.7.10.2]
K06279  SHC1; SHC-transforming protein 1
K07593  SLC2A2, GLUT2; MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 2
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K08521  LHB; lutropin subunit beta
K08522  CGA; glycoprotein hormones alpha chain
K08550  ESR1, NR3A1; estrogen receptor alpha
K08551  ESR2, NR3A2; estrogen receptor beta
K09408  FOXO3; forkhead box protein O3
K09444  IRF1; interferon regulatory factor 1
K10151  CCND2; G1/S-specific cyclin-D2
K11220  STAT1; signal transducer and activator of transcription 1
K11223  STAT5A; signal transducer and activator of transcription 5A
K11224  STAT5B; signal transducer and activator of transcription 5B
K12407  GCK; glucokinase [EC:2.7.1.2]
K17101  ELF5; E74-like factor 5
K17106  WAP; whey acidic protein
K17107  CSN2; beta-casein
K17447  SHC2; SHC-transforming protein 2
K17448  SHC3; SHC-transforming protein 3
K17449  SHC4; SHC-transforming protein 4
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