Signaling lymphocytic activation molecule 1 is a
protein that in humans is encoded by the SLAMF1gene.[5][6] Recently SLAMF1 has also been designated CD150 (
cluster of differentiation 150).
The
gene encoding SLAMF1
receptor is located on the human
chromosome 1. It consists of eight
exons and seven
introns.
Alternative splicing of SLAMF1 transcripts results in several
isoforms of the
protein, including the conventional transmembrane isoform (mCD150), secreted isoform (sCD150) cytoplasmic isoform (cCD150), and the novel transmembrane isoform (nCD150).[7]
SLAMF1 is a type I
transmembrane protein belonging to the
immunoglobulin superfamily.[8] Its molecular weight is between 70 kDa and 95 kDa. The extracellular region of the
receptor is composed of one Ig variable-like
domain and one Ig constant 2-like
domain. The intracellular region of the
receptor contains two intracellular tyrosine-based switch motives (ITSMs) that interact with
SH2 domain-containing
proteins. However, nCD150 intracellular region differs from other
isoforms of this
protein, it lacks ITSMs. sCD150 isoform lacks the
transmembrane domain and therefore, it can not be anchored to the
cell membrane.[7]
SH2 domain-containing
proteins, specifically
adaptor proteinsSAP and
EAT-2, and
phosphatasesSHP-1,
SHP-2 and
SHIP, interact with ITSMs in the intracellular region of SLAMF1.[7][10] Binding of
SAP to ITSMs leads to the activation of the
kinaseFyn that phosphorylates
tyrosines of SLAMF1 and recruits downstream
signalingproteins. Because of the high affinity of
SAP to
tyrosine phosphorylated ITSMs, it outcompetes the
phosphatases which are the mediators of the inhibitory signal. Therefore, the expression and availability of
SAP play a crucial role in the determination of the type of the signal.[11][12]
The development of
NKT cells is dependent on a signal mediated by
SAP. It was found out that the homophilic interaction of SLAMF1 or SLAMF6 is required for
SAP recruitment in
NKT cells. This interaction mediates a secondary signal crucial for
NKT celldifferentiation and expansion in the
thymus.[13]
SLAMF1 expression in
macrophages is associated with killing of
Gram-negative bacteria. SLAMF1 acts as a bacterial sensor. It is internalized after the recognition of
Gram-negative bacteria, and it plays a role in the regulation of
phagosome maturation,
ROS and
NO production. The absence of SLAMF1 in
phagocytes leads, among other things, to the disruption of
cytokine production.[13]
^Schwartz AM, Putlyaeva LV, Covich M, Klepikova AV, Akulich KA, Vorontsov IE, et al. (October 2016). "Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1859 (10): 1259–1268.
doi:
10.1016/j.bbagrm.2016.07.004.
PMID27424222.
^Wu N, Veillette A (February 2016). "SLAM family receptors in normal immunity and immune pathologies". Current Opinion in Immunology. 38: 45–51.
doi:
10.1016/j.coi.2015.11.003.
PMID26682762.
Sayos J, Wu C, Morra M, Wang N, Zhang X, Allen D, et al. (October 1998). "The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM". Nature. 395 (6701): 462–469.
Bibcode:
1998Natur.395..462S.
doi:
10.1038/26683.
PMID9774102.
S2CID4324402.
Rogge L, Bianchi E, Biffi M, Bono E, Chang SY, Alexander H, et al. (May 2000). "Transcript imaging of the development of human T helper cells using oligonucleotide arrays". Nature Genetics. 25 (1): 96–101.
doi:
10.1038/75671.
PMID10802665.
S2CID5449948.
Murabayashi N, Kurita-Taniguchi M, Ayata M, Matsumoto M, Ogura H, Seya T (July 2002). "Susceptibility of human dendritic cells (DCs) to measles virus (MV) depends on their activation stages in conjunction with the level of CDw150: role of Toll stimulators in DC maturation and MV amplification". Microbes and Infection. 4 (8): 785–794.
doi:
10.1016/S1286-4579(02)01598-8.
PMID12270725.
Ferrand V, Li C, Romeo G, Yin L (May 2003). "Absence of SLAM mutations in EBV-associated lymphoproliferative disease patients". Journal of Medical Virology. 70 (1): 131–136.
doi:
10.1002/jmv.10373.
PMID12629654.
S2CID44309832.