Protein found in humans
CD244 (C luster ofD ifferentiation 244) also known as 2B4 or SLAMF4 is aprotein that in humans is encoded by the CD244gene .[ 5]
CD244 is atype-I transmembrane protein belonging to thesignaling lymphocytic activation molecule family of receptors (SLAMF) which are expressed in different types ofhematopoietic cells .[ 6] immune system .[ 7]
A ligand of CD244 isCD48 (SLAMF2).CD48 also belongs to theSLAMF , it does not have an intracellulardomain and it is anchored to theplasma membrane by aGPI-anchor .[ 6] receptors from theSLAMF mediate heterophilic interactions.[ 8] [ 7]
Thereceptor CD244 is encoded by theCD244 gene located on the long arm of humanchromosome 1 .[ 8] isoforms have been found for thisgene .[ 9] NK cells but it is also expressed inmonocytes ,basophils ,eosinophils ,mast cells ,dendritic cells , andT cells .[ 8] [ 10]
Thereceptor is composed of intracellular, transmembrane, and extracellulardomains . The intracellulardomain contains four intracellular tyrosine-based switch motives (ITSMs) and interacts withSH2 domain -containingproteins which are involved in thesignaling and determine whether it will be activating or inhibitory.[ 9] [ 6] domain and one Ig constant 2-likedomain .[ 10] [ 6]
CD244 can function as an activating or inhibitoryreceptor . The expression and availability of an adaptor proteinSAP determine whether the signal is activating or inhibitory.[ 9] phosphatases SHP1 ,SHP2 ,SHIP-1 or thekinase CsK on the third ITSM.[ 6] signaling is associated with the adaptor proteinSAP .[ 9] SAP binds to phosphorylated tyrosines in ITSMs. Then it binds to thekinase Fyn and that enhances downstreamsignaling .[ 11] [ 9]
CD244 is expressed in all types ofNK cells ,[ 9] cytotoxicity andIFNγ production.[ 9] [ 6] CD8+ T cells [ 9] signaling via CD244 enhances theirproliferation andcytotoxic effect .[ 6]
Role of CD244 in viral infections [ edit ] NK cells andCD8+ T cells play a crucial role in antiviral immunity. The activatingsignaling via CD244 leads to the enhancement of their cytolytic activity that they use for killing infectedcells .[ 7] SAP is decreased during some chronicviral infections , such asHIV ,HBV andHCV , and that is associated with the inhibitory signal and the exhaustion ofCD8+ T cells .[ 7] [ 9]
Role of CD244 in cancer [ edit ] NK cells ,T cells ,dendritic cells , andmyeloid-derived suppressor cells in thetumor microenvironment express CD244.[ 7] SAP . However, inhibitorysignaling has been shown to predominate in the tumor-associatedimmune cells .[ 10]
NK cells andCD8+ T cells use their cytolytic activity to kill tumorcells . Increased CD244 expression in thesecells is associated with the inhibitory signal and the exhaustion of thecells . That leads to the impaired antitumor immunity caused by decreasedcytotoxicity andproliferation ofNK cells andCD8+ T cells .Dendritic cells are importantantigen presenting cells . CD244 expression indendritic cells is also associated with the inhibitory signal due to the low expression ofSAP and therefore, they have decreased production ofproinflammatory cytokines and reduced ability to activateNK cells andT cells .Myeloid-derived suppressor cells are suppressivecells also found in tumors. Their increased number in the tumor is associated with the progression of the disease. It is known that CD244signaling in thesecells enhances their immunosuppressive capacity resulting in the reducedimmune response against tumors.[ 9]
^a b c GRCh38: Ensembl release 89: ENSG00000122223 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000004709 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Entrez Gene: CD244 CD244 molecule, natural killer cell receptor 2B4" .^a b c d e f g Pahima H, Puzzovio PG, Levi-Schaffer F (July 2019). 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