P17777
uniprot
P17777
canonical
amino_acid_sequence
MKVLAAGIVPLLLILHWKHGAGSPLPITPVNATCAIRHPCHGNLMNQIKSQLAQLNGSANALFISYYTAQGEPFPNNVDKLCAPNMTDFPPFHANGTEKTKLVELYRMVTYLGASLTNITWDQKNLNPTAVSLQIKLNATTDVMRGLLSSVLCRLCNKYHVGHVDVPCVPDNSSKEAFQRKKLGCQLLGTYKQVISVLAQAF
uniprot
proteins
function
FUNCTION: Functions as a cytokine that binds to the LIF receptor complex. The LIF receptor complex indeed consists of two signaling receptor subunits IL6ST/gp130 and LIFR that transduce the signal into the cell (By similarity). Functionally, regulates cell self-renewal, differentiation and survival of embryonic stem cells (ESCs) (PubMed:2512641, PubMed:3143917). Also 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. These kinases subsequently phosphorylate IL6ST/gp130 and LIFR. 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). 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. Tyrosine phosphorylation of the p85 subunit of PI(3)K by JAK1 leads to activation of the serine/ threonine kinase AKT (protein kinase B) (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P09056, ECO:0000250|UniProtKB:P15018, ECO:0000269|PubMed:2512641, ECO:0000269|PubMed:3143917}.
uniprot
proteins
mass_dalton
22113
uniprot
proteins
protein_family
LIF/OSM family
uniprot
proteins
pubmed
2512641
uniprot
proteins
pubmed
3143917
uniprot
proteins
sequence_length
202
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P15018}.
uniprot
proteins