The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor has been found to be essential in mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis.
CD40 is a Type I Transmembrane Glycoprotein that belongs to the TNF Receptor Superfamily. CD40 is expressed in B cells; follicular dendritic cells; dendritic cells; activated monocytes; macrophages; endothelial cells; vascular smooth muscle cells; and several tumor cell lines. The extracellular domain of CD40 is characterized by Cysteine rich repeat regions. Interaction of CD40 with its ligand (CD40L) leads to aggregation of CD40 molecules; which in turn interact with cytoplasmic components to initiate signaling pathways. Several different TRAF proteins (adaptor proteins) have been identified to serves as mediators of the signal transduction. CD40 plays an essential role in mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching; memory B cell development; and germinal center formation.
CD44 is a cell-surface receptor for hyaluronic acid and also interacts with other ligands; such as osteopontin; collagens; and matrix metalloproteinases. A large number of CD44 isoforms can be generated by the insertion of different combinations of at least nine exons. Increased CD44 antigen is associated with relapses in non-small cell lung cancers. Furthermore; an increasing quantity of evidence suggests that CD44 has various functions related to inflammatory disease. CD44 deficiency induces severe liver injury. CD44-hyaluronate mediates in lymphocyte T and monocyte adhesion to the endothelium; stimulates proinflammatory cytokine release from macrophages and participates in dedifferentiation phenotype of smooth muscle cells from contractile state to synthetic one.
CD44 is a type I transmembrane protein and a member of the cartilage link protein family. It is involved in cell-cell and cell-matrix interactions and signal transduction. Several CD44 ligands have been identified. The most extensively characterized ligand for CD44 is hyaluronan, a component of the extracellular matrix. CD44 protein is expressed on the majority of immune cells. The binding of CD44 to hyaluronan is induced on T lymphocytes after activation by antigen and on monocytes after stimulation by inflammatory agents. Under inflammatory conditions, CD44 on endothelial cells presents hyaluronan to CD44 on activated T lymphocytes and mediates a rolling interaction under flow conditions. Perturbations of the hyaluronan-CD44 interaction at the plasma membrane by various antagonists result in attenuation of receptor tyrosine kinase and transporter activities and inhibition of tumor progression in vivo. CD44 is known to interact with the ezrin family (ERM family) members and form a complex that plays diverse roles within both normal and abnormal cells, particularly cancer cells. CD44 and ezrin and their respective complex have properties sμggesting that they may be important in the process of tumour-endothelium interactions, cell migrations, cell adhesion, tumour progression and metastasis.
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