Entry
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
BRITE hierarchy
Pathway map
Ortholog table
Network
Element
N00920 PRL-JAK-STAT signaling pathway
Drug
D00780 Bromocriptine mesylate (USP)
D00987 Cabergoline (JP18/USP/INN)
D03165 Bromocriptine (USAN/INN)
D11961 Giredestrant (USAN/INN)
D12628 Vepdegestrant (JAN/USAN/INN)
D12827 Palazestrant (USAN/INN)
D12943 Giredestrant tartrate (JAN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
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 ]
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 ]
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
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 ]
1081 CGA; glycoprotein hormones, alpha polypeptide [KO:K08522 ]
3972 LHB; luteinizing hormone subunit beta [KO:K08521 ]
3973 LHCGR; luteinizing hormone/choriogonadotropin receptor [KO:K04248 ]
3659 IRF1; interferon regulatory factor 1 [KO:K09444 ]
6514 SLC2A2; solute carrier family 2 member 2 [KO:K07593 ]
Compound
C00355 3,4-Dihydroxy-L-phenylalanine
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Binart N, Bachelot A, Bouilly J
Title
Impact of prolactin receptor isoforms on reproduction.
Journal
Reference
Authors
Bachelot A, Binart N
Title
Reproductive role of prolactin.
Journal
Reference
Authors
Hennighausen L, Robinson GW
Title
Information networks in the mammary gland.
Journal
Reference
Authors
Bouilly J, Sonigo C, Auffret J, Gibori G, Binart N
Title
Prolactin signaling mechanisms in ovary.
Journal
Reference
Authors
Oakes SR, Rogers RL, Naylor MJ, Ormandy CJ
Title
Prolactin regulation of mammary gland development.
Journal
Reference
Authors
Frasor J, Gibori G
Title
Prolactin regulation of estrogen receptor expression.
Journal
Reference
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
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
Reference
Authors
Grattan DR, Kokay IC
Title
Prolactin: a pleiotropic neuroendocrine hormone.
Journal
Reference
Authors
Yu-Lee LY, Luo G, Book ML, Morris SM
Title
Lactogenic hormone signal transduction.
Journal
Reference
Authors
Tam SP, Lau P, Djiane J, Hilton DJ, Waters MJ
Title
Tissue-specific induction of SOCS gene expression by PRL.
Journal
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
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
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
Related pathway
KO pathway
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