LIF
entrez
3976
canonical
uniprot
P15018
canonical
ensembl
ENSG00000128342
resolver
ensp
ENSP00000249075
resolver
ensp
ENSP00000384450
resolver
genesymbol
LIF
resolver
genesymbol_syn
HILDA
resolver
hgnc
HGNC:6596
resolver
uniprot
B2RCW7
resolver
uniprot
B5MC23
resolver
uniprot
Q52LZ2
resolver
uniprot_entry
LIF_HUMAN
resolver
uniprot_sec
B2RCW7
resolver
uniprot_sec
B5MC23
resolver
uniprot_sec
Q52LZ2
resolver
amino_acid_sequence
MKVLAAGVVPLLLVLHWKHGAGSPLPITPVNATCAIRHPCHNNLMNQIRSQLAQLNGSANALFILYYTAQGEPFPNNLDKLCGPNVTDFPPFHANGTEKAKLVELYRIVVYLGTSLGNITRDQKILNPSALSLHSKLNATADILRGLLSNVLCRLCSKYHVGHVDVTYGPDTSGKDVFQKKKLGCQLLGKYKQIIAVLAQAF
uniprot
proteins
function
FUNCTION: Functions as a cytokine that binds to the LIF receptor complex (PubMed:11294841, PubMed:14527405, PubMed:36930708). The LIF receptor complex indeed consists of two signaling receptor subunits IL6ST/gp130 and LIFR that transduce the signal into the cell (PubMed:14527405, PubMed:36930708). Functionally, regulates cell self-renewal, differentiation and survival of embryonic stem cells (ESCs) and is crucial for embryonic implantation (By similarity). Mechanistically, ligand binding to LIFR, induces heterodimerization with IL6ST/gp130 activating JAK tyrosine kinases (JAK1 or JAK2 and to a lesser extent TYK2) bound to their intracellular domains (PubMed:11294841). These kinases subsequently phosphorylate IL6ST/gp130 and LIFR (PubMed:11294841). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducers and activators of transcription (STAT3 and to lesser extent STAT1) (PubMed:11294841). In parallel to the activation of the STAT3-pathway, the binding of LIF to the LIF receptor complex leads to the activation of the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI(3)K) pathways (PubMed:11294841). Tyrosine phosphorylation of the p85 subunit of PI(3)K by JAK1 leads to activation of the serine/ threonine kinase AKT (protein kinase B) (PubMed:11294841). PI(3)K-dependent signaling is required for efficient self-renewal of murine ES cells, and regulation of ERK activity is functionally important in this response (By similarity). Moreover, induces tyrosine phosphorylation of PTPN11, that associates with IL6ST/gp130-LIFR, which in turn recruits the p85 regulatory subunit of PI(3)K protein kinase, promoting PI3K-AKT activation, and GRB2-RAS-MAPK signaling (PubMed:11294841). {ECO:0000250|UniProtKB:P09056, ECO:0000250|UniProtKB:P17777, ECO:0000269|PubMed:11294841, ECO:0000269|PubMed:14527405, ECO:0000269|PubMed:36930708}.
uniprot
proteins
mass_dalton
22008
uniprot
proteins
protein_family
LIF/OSM family
uniprot
proteins
pubmed
10591208
uniprot
proteins
pubmed
11294841
uniprot
proteins
pubmed
14527405
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15146197
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1692837
uniprot
proteins
pubmed
17652170
uniprot
proteins
pubmed
2475312
uniprot
proteins
pubmed
2730639
uniprot
proteins
pubmed
3128791
uniprot
proteins
pubmed
3143918
uniprot
proteins
pubmed
36930708
uniprot
proteins
pubmed
8489250
uniprot
proteins
sequence_length
202
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:11294841}.
uniprot
proteins