KEGG   PATHWAY: hsa04917
hsa04917                    Pathway                                
Prolactin signaling pathway - Homo sapiens (human)
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.
Organismal Systems; Endocrine system
Pathway map
hsa04917  Prolactin signaling pathway

nt06325  Hormone/cytokine signaling
N00920  PRL-JAK-STAT signaling pathway
D00780  Bromocriptine mesylate (USP)
D00987  Cabergoline (JP18/USP/INN)
D01348  Terguride (JAN/INN)
D03165  Bromocriptine (USAN/INN)
D06631  Prinaberel (USAN/INN)
D12628  Vepdegestrant (USAN/INN)
Other DBs
GO: 0038161
Homo sapiens (human) [GN:hsa]
5617  PRL; prolactin [KO:K05439]
5618  PRLR; prolactin receptor [KO:K05081]
3717  JAK2; Janus kinase 2 [KO:K04447] [EC:]
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:]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
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:]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
2309  FOXO3; forkhead box O3 [KO:K09408]
2592  GALT; galactose-1-phosphate uridylyltransferase [KO:K00965] [EC:]
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:]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
2353  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:]
595  CCND1; cyclin D1 [KO:K04503]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
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:]
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:]
6514  SLC2A2; solute carrier family 2 member 2 [KO:K07593]
2645  GCK; glucokinase [KO:K12407] [EC:]
894  CCND2; cyclin D2 [KO:K10151]
3630  INS; insulin [KO:K04526]
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
Binart N, Bachelot A, Bouilly J
Impact of prolactin receptor isoforms on reproduction.
Trends Endocrinol Metab 21:362-8 (2010)
Bachelot A, Binart N
Reproductive role of prolactin.
Reproduction 133:361-9 (2007)
Hennighausen L, Robinson GW
Information networks in the mammary gland.
Nat Rev Mol Cell Biol 6:715-25 (2005)
Bouilly J, Sonigo C, Auffret J, Gibori G, Binart N
Prolactin signaling mechanisms in ovary.
Mol Cell Endocrinol 356:80-7 (2012)
Oakes SR, Rogers RL, Naylor MJ, Ormandy CJ
Prolactin regulation of mammary gland development.
J Mammary Gland Biol Neoplasia 13:13-28 (2008)
Frasor J, Gibori G
Prolactin regulation of estrogen receptor expression.
Trends Endocrinol Metab 14:118-23 (2003)
Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA
Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice.
Endocr Rev 19:225-68 (1998)
Weinhaus AJ, Stout LE, Bhagroo NV, Brelje TC, Sorenson RL
Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for increasing glucose-stimulated insulin secretion during pregnancy.
J Endocrinol 193:367-81 (2007)
Grattan DR, Kokay IC
Prolactin: a pleiotropic neuroendocrine hormone.
J Neuroendocrinol 20:752-63 (2008)
Yu-Lee LY, Luo G, Book ML, Morris SM
Lactogenic hormone signal transduction.
Biol Reprod 58:295-301 (1998)
Tam SP, Lau P, Djiane J, Hilton DJ, Waters MJ
Tissue-specific induction of SOCS gene expression by PRL.
Endocrinology 142:5015-26 (2001)
Halperin J, Devi SY, Elizur S, Stocco C, Shehu A, Rebourcet D, Unterman TG, Leslie ND, Le J, Binart N, Gibori G
Prolactin signaling through the short form of its receptor represses forkhead transcription factor FOXO3 and its target gene galt causing a severe ovarian defect.
Mol Endocrinol 22:513-22 (2008)
Sakamoto K, Creamer BA, Triplett AA, Wagner KU
The Janus kinase 2 is required for expression and nuclear accumulation of cyclin D1 in proliferating mammary epithelial cells.
Mol Endocrinol 21:1877-92 (2007)
Oakes SR, Hilton HN, Ormandy CJ
The alveolar switch: coordinating the proliferative cues and cell fate decisions that drive the formation of lobuloalveoli from ductal epithelium.
Breast Cancer Res 8:207 (2006)
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

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