KEGG   PATHWAY: mmu04917
Entry
mmu04917                    Pathway                                
Name
Prolactin signaling pathway - Mus musculus (house mouse)
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
mmu04917  Prolactin signaling pathway
mmu04917

Other DBs
GO: 0038161
Organism
Mus musculus (house mouse) [GN:mmu]
Gene
19109  Prl; prolactin [KO:K05439]
19111  Prl6a1; prolactin family 6, subfamily a, member 1 [KO:K05439]
28078  Prl5a1; prolactin family 5, subfamily a, member 1 [KO:K05439]
19116  Prlr; prolactin receptor [KO:K05081]
16452  Jak2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
20416  Shc1; src homology 2 domain-containing transforming protein C1 [KO:K06279]
216148  Shc2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447]
20418  Shc3; src homology 2 domain-containing transforming protein C3 [KO:K17448]
271849  Shc4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449]
20779  Src; Rous sarcoma oncogene [KO:K05704] [EC:2.7.10.2]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
56484  Foxo3; forkhead box O3 [KO:K09408]
14430  Galt; galactose-1-phosphate uridyl transferase [KO:K00965] [EC:2.7.7.12]
14784  Grb2; growth factor receptor bound protein 2 [KO:K04364]
20662  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
20663  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
14281  Fos; FBJ osteosarcoma oncogene [KO:K04379]
26419  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
26420  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
26414  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
26416  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
19094  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
29857  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
26415  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
12443  Ccnd1; cyclin D1 [KO:K04503]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
12700  Cish; cytokine inducible SH2-containing protein [KO:K04701]
12703  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
216233  Socs2; suppressor of cytokine signaling 2 [KO:K04695]
12702  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
67296  Socs4; suppressor of cytokine signaling 4 [KO:K04697]
56468  Socs5; suppressor of cytokine signaling 5 [KO:K04698]
192157  Socs7; suppressor of cytokine signaling 7 [KO:K04699]
54607  Socs6; suppressor of cytokine signaling 6 [KO:K04699]
20846  Stat1; signal transducer and activator of transcription 1 [KO:K11220]
20848  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
20850  Stat5a; signal transducer and activator of transcription 5A [KO:K11223]
20851  Stat5b; signal transducer and activator of transcription 5B [KO:K11224]
21943  Tnfsf11; tumor necrosis factor (ligand) superfamily, member 11 [KO:K05473]
21934  Tnfrsf11a; tumor necrosis factor receptor superfamily, member 11a, NFKB activator [KO:K05147]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
22373  Wap; whey acidic protein [KO:K17106]
13711  Elf5; E74-like factor 5 [KO:K17101]
12991  Csn2; casein beta [KO:K17107]
12640  Cga; glycoprotein hormones, alpha subunit [KO:K08522]
16866  Lhb; luteinizing hormone beta [KO:K08521]
16867  Lhcgr; luteinizing hormone/choriogonadotropin receptor [KO:K04248]
13074  Cyp17a1; cytochrome P450, family 17, subfamily a, polypeptide 1 [KO:K00512] [EC:1.14.14.19 1.14.14.32]
13982  Esr1; estrogen receptor 1 (alpha) [KO:K08550]
13983  Esr2; estrogen receptor 2 (beta) [KO:K08551]
16362  Irf1; interferon regulatory factor 1 [KO:K09444]
21823  Th; tyrosine hydroxylase [KO:K00501] [EC:1.14.16.2]
20526  Slc2a2; solute carrier family 2 (facilitated glucose transporter), member 2 [KO:K07593]
103988  Gck; glucokinase [KO:K12407] [EC:2.7.1.2]
12444  Ccnd2; cyclin D2 [KO:K10151]
16334  Ins2; insulin II [KO:K04526]
16333  Ins1; insulin I [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
mmu04010  MAPK signaling pathway
mmu04151  PI3K-Akt signaling pathway
mmu04630  JAK-STAT signaling pathway
mmu04728  Dopaminergic synapse
mmu04911  Insulin secretion
mmu04913  Ovarian steroidogenesis
mmu04915  Estrogen signaling pathway
KO pathway
ko04917   
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