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ORGANELLE MARKERS - Plasma membrane




CD40 is a 45-50 kDa type I membrane protein and a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also known as pb50 or CDW40. CD40 is expressed primarily by professional antigen-presenting cells and it is also expressed on nonimmune cell types. The CD40 expressed by professional antigen-presenting cells plays a critical role in costimulation and antigen-presenting cell activation in T cell-dependant immune responses. Signals generated through CD40 in B cells are antiapoptotic. These signals are also required for T cell-dependant B cell activation and proliferation, isotype switching, up-regulation of costimulatory receptors, germinal center formation and memory generation. CD40 signal transduction is initiated by binding trimeric CD40 ligand (CD40L) which is found on the surface of activated T cells. CD40 engages several signalling pathways in B cells and these include NF-kappaB, the mitogen-activated protein kinases p38 and c-Jun N-terminal kinase. The 62 amino acid cytoplasmic domain (CD40c) of CD40 contains two linear TNF-receptor associated factor (TRAF) binding domains. The membrane proximal site of CD40c binds TRAF6 and the membrane distal site binds TRAF1, 2 and 3. CD40c is thought to mediate the CD40-dependant signaling pathways by recruitment of TRAF to this multimerized domain . CD40 ligation has also been shown to stimulate iNOS expression, and therefore NO production, by activating NF-kappaB in IFN-?treated microglial cells . NO derived from microglia has been implicated in the damage of myelin-producing oligodendrocytes in demyelating disorders like multiple sclerosis (MS) and neuronal death during Alzheimer.s disease and brain trauma. Increased CD40-CD40 ligation has beenimplicated in the pathogenesis of several autoimmune inflammatory diseases, such as MS, arthritis and insulin-dependant diabetes.


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