HGNC Approved Gene Symbol: ICAM2
Cytogenetic location: 17q23.3 Genomic coordinates (GRCh38): 17:64,002,595-64,020,633 (from NCBI)
LFA1 (153370/600065) is a receptor for intercellular adhesion molecule-1 (ICAM1; 147840), a surface molecule that is constitutively expressed on some tissues and induced on others in inflammation. Several lines of evidence suggested the existence of a second LFA1 ligand. Staunton et al. (1989) cloned this second ligand, designated ICAM2, using a novel method for identifying ligands of adhesion molecules. They found that ICAM2 is an integral membrane protein that has 2 immunoglobulin-like domains, unlike ICAM1, which has 5.
By screening for genes involved in the regulation of apoptosis, Perez et al. (2002) recovered a cDNA encoding ICAM2. Through interaction with LFA1, ICAM2 mediates a block of apoptosis by activation of the phosphatidylinositol 3-kinase (PI3K; see 601232)/AKT (164730) pathway. ICAM2 induces phosphorylation of ezrin (VIL2; 123900), phosphatidylinositol-dependent kinase-1 (PDK1; 605213) activation, and PI3K and AKT membrane translocation. Subsequently, the AKT targets BAD (603167), glycogen synthase kinase-3 (GSK3; see 606784), and FKHR (136533) are also phosphorylated. Flow cytometric analysis demonstrated that ICAM2 clustering leads to phosphatidylinositol 3,4,5 production and AKT activity in primary CD19 (107265)-positive B cells, protecting them from FAS (134637)- and tumor necrosis factor (TNF; 191160)-mediated apoptosis. Perez et al. (2002) proposed that ICAM2 or other adhesion molecules could be alternative targets in the development of antitumor therapies.
Sansom et al. (1991) used a panel of somatic cell hybrids and chromosome-mediated gene transfectants to demonstrate that the ICAM2 gene maps to 17q23-q25.
Perez, O. D., Kinoshita, S., Hitoshi, Y., Payan, D. G., Kitamura, T., Nolan, G. P., Lorens, J. B. Activation of the PKB/AKT pathway by ICAM-2. Immunity 16: 51-65, 2002. [PubMed: 11825565] [Full Text: https://doi.org/10.1016/s1074-7613(02)00266-2]
Sansom, D., Borrow, J., Solomon, E., Trowsdale, J. The human ICAM2 gene maps to 17q23-25. Genomics 11: 462-464, 1991. [PubMed: 1769660] [Full Text: https://doi.org/10.1016/0888-7543(91)90157-a]
Staunton, D. E., Dustin, M. L., Springer, T. A. Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1. Nature 339: 61-64, 1989. [PubMed: 2497351] [Full Text: https://doi.org/10.1038/339061a0]