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 SAPtotyrosine 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.
