Disease relevance of CD244

• The cytoplasmic domain of 2B4 associates with src homology 2 domain-containing protein or signaling lymphocyte activation molecule-associated protein, whose mutation is the underlying genetic defect in the X-linked lymphoproliferative syndrome [1].
• An increased expression of CD94, CD244, and perforin, which was the consequence of the expansion of the CD8(bright)CD28 negative T-cell subset, was also observed in HIV infection [2].
• There were significantly more lymphocytes expressing CD8 and CD244/CD8 in patients with severe sore throat [3].
• CD48, the natural ligand of 2B4, is highly expressed on the surface of EBV(+) B cell lines [4].
• In melanoma patients, Melan-A-specific T cells up-regulated 2B4 in parallel with in vivo differentiation [5].
• 2B4+CD8+ T cells play inhibitory role aganist constrained HIV epitopes [6].

Psychiatry related information on CD244

• For the 14 subjects who completed the study, clomipramine hydrochloride (mean +/- SD dose, 120 +/- 48 mg/d) was superior to desipramine hydrochloride (mean +/- SD dose, 135 +/- 53 mg/d) in decreasing nail biting as measured by a repeated-measures analysis of variance on the Nail Biting Severity, Nailbiting Impairment, and Clinical Progress scales [7].

High impact information on CD244

• Engagement of receptor 2B4 by CD48 on insect cells induced weak polarization and no degranulation [8].
• However, coengagement of 2B4 and CD16 by their respective ligands resulted in granule polarization and cytotoxicity in the absence of leukocyte functional antigen-1-mediated adhesion to target cells [8].
• Two papers describing mice deficient in signaling lymphocyte activation molecule and 2B4 represent the first accounts of immune phenotypes in animals lacking members of the SLAM family of receptors [9].
• Binding of activation receptor 2B4 to its ligand CD48 was not sufficient for Vav1 phosphorylation [10].

Chemical compound and disease context of CD244

• Analysis of Northern blots showed that none of the prostate cancer cell lines (LNCaP, C4, C4-2, C4-2B4, 9069E3, DU145, and PC3) expressed IGFBP-rP1 mRNA [11].
• RESEARCH DESIGN AND METHODS: Nail samples from 184 diabetic patients who exhibited symptoms consistent with toenail onychomycosis were screened for dermatophyte fungal infection using DTM, potassium hydroxide evaluation, and central mycology laboratory culture tests [12].
• The interactions between UDP-glucuronic acid and two human liver UDP-glucuronosyltransferase 2B4 peptides (14-150 and 299-446) purified from E. coli as Staphylococcus aureus protein A fusion proteins have been investigated [13].
• The Titanium Elastic Nail (TEN) offers a number of potential advantages over traditional ways of treating long bone fractures particularly in the paediatric population [14].

Biological context of CD244

• CD244-3BP2 interaction was direct and regulated by phosphorylation, as shown by a three-hybrid analysis in yeast and NK cells [15].
• It binds a protein termed Src homology 2 domain-containing protein (SH2D1A) or signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), which in turn has been proposed to function as a regulator of the 2B4-associated signal transduction pathway [4].
• Human 2B4 was cloned based on sequence homology with mouse 2B4 [16].
• Our results show that NK-resistant CC were sensitive to lysis by unstimulated peripheral blood lymphocytes in the presence of phytohemagglutin (PHA), to antibody-dependent cell cytotoxicity in presence of anti-Tja antibodies, and to monoclonal antibody redirected killing using anti-TR antibodies anti-CD16 and anti-CD244/2B4 [17].
• However, when we introduced a three-base substitution mutation to disrupt the activator protein-1 binding site at (-106 to -100) in the 2B4 promoter, we found complete loss of transcriptional activity, including the two-fold increase due to PMA induction of PKC [18].

Anatomical context of CD244

• Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244) [19].
• In mice and rats, CD2 and CD244 (2B4), which are expressed predominantly on T cells and natural killer cells, respectively, bind the same, broadly expressed ligand, CD48 [20].
• CD244, a member of the CD150 family, is a cell surface protein expressed on NK, CD8+ T, and myeloid cells [15].
• 2B4 (CD244) is expressed and functional on human eosinophils [21].
• B cell induction of IL-13 expression in NK cells: role of CD244 and SLAM-associated protein [22].

Associations of CD244 with chemical compounds

• The cell surface glycoprotein 2B4 (CD244) of the Ig superfamily is involved in the regulation of NK and T lymphocyte functions [1].
• To determine the structural basis for 2B4/CD48 interaction, selected amino acid residues in the V domain of the human 2B4 (h2B4) were mutated to alanine by site-directed mutagenesis [23].
• NK cell inhibitory receptors prevent tyrosine phosphorylation of the activation receptor 2B4 (CD244) [24].
• Association of the X-linked lymphoproliferative disease gene product SAP/SH2D1A with 2B4, a natural killer cell-activating molecule, is dependent on phosphoinositide 3-kinase [25].
• Treatment with the PKC inhibitor, bisindolylmaleimide I (Gö6850), of YT cells or YT cells depleted of Ca2+-dependent isoforms of PKC prior to 2B4 stimulation, resulted in inhibition of natural cytotoxicity and redirected antibody-dependent cellular cytotoxicity [18].

Physical interactions of CD244

• 3BP2 interacts with human but not murine CD244 [15].
• Human CD48 bound human 2B4 with a similar affinity (Kd approximately 8 microM) [26].
• Signaling lymphocyte activation molecule-associated protein (SAP) can bind to all 4 ITSMs of 2B4 in a phosphorylation-dependent manner [19].

Enzymatic interactions of CD244

• In this report, we show that NK cells from individuals with XLP but not healthy individuals fail to phosphorylate and thereby inactivate glycogen synthase kinase-3 (GSK-3) following 2B4 stimulation [27].
• Human 2B4 became tyrosine phosphorylated following pervanadate-treatment of transfected cells and recruited SHP-2 [28].

Regulatory relationships of CD244

• Instead, 2B4 is activated by binding to CD48, a GPI-anchored surface molecule that is widely expressed in the hemopoietic system [29].
• 2B4-expressing target cells can efficiently stimulate NK cell cytotoxicity and IFN-gamma production [29].
• In IL-2-activated NK cells with high SAP expression the triggering of 2B4 alone is sufficient to induce NK cell cytotoxicity, demonstrating a correlation between the regulated SAP expression and the function of 2B4 [30].
• The data are consistent with a model in which the mechanism of signal transduction by CD244 is to regulate FYN kinase recruitment and/or activity and the outcome of CD48/CD244 interactions is determined by which other receptors are engaged [31].

Other interactions of CD244

• We have recently identified CD48 as the high affinity counterreceptor for 2B4 in both mice and humans [1].
• Thus, the positive signals attributed to the B cell activation of CD244 on murine NK cells appears to be more similar to the activity of CD244 on human cells [22].
• 2B4 (CD244), a member of the CD2 subset of the Ig superfamily receptors, is expressed on all human NK cells, a subpopulation of T cells, basophils and monocytes [32].
• Expression and regulation of the SLAM-family receptors SLAM, CD84, and 2B4, as well as the lytic effectors perforin and granzyme-B are normal in SAP-deficient CTLs [33].
• Thus, cross-linking of 2B4 resulted in inhibition of both cytolytic activity and interferon-gamma (IFN-gamma) production [34].

Analytical, diagnostic and therapeutic context of CD244

• This enhancement was concomitant with an increase in cytotoxicity due to CD244 ligation [15].
• In this study, we report the molecular cloning and characterization of the human 2B4 (h2B4) promoter [1].
• We isolated h2B4 genomic clones and PCR amplified the 5' untranslated region containing the promoter elements [1].
• Two NK-related receptors showed significantly different levels of expression in heart transplant recipients: the cytotoxic effector, CD244, which was in a significantly increased proportion on T and NKT-like cells; and the activating receptor, CD161, which was expressed significantly less on NK and NKT-like cells, but more on T cells [35].
• Molecular dissection of 2B4 signaling: implications for signal transduction by SLAM-related receptors [36].

References