ORGANELLE MARKERS - Plasma membrane

CD40

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.

back

CD40 Ligand

CD40 ligand (CD40L), also known as CD154, gp39 and TRAP, is a 33 kDa type II membrane glycoprotein expressed mainly on the cell surface of activated T lymphocytes but also exists as a soluble form extracellularly. CD40L is the ligand for CD40, a member of the TNF superfamily, which is expressed on the cell surface of B cells, macrophages/monocytes, dendritic cells, vascular endothelial cells, and epithelial cells. CD40L plays an important role in B cell proliferation, antibody class switching, modulation of apoptosis in the germinal center through interaction with B cells expressing CD40, and activation of CD4+ T cells. Mutation within the CD40L gene is linked to hyper IgM syndrome, an Xlinked immunodeficiency disease that is characterized by elevated level of serum IgM and decreased level of other isotypes.

back

Fas/APO-1

Fas/APO-1/CD95 is a 36 kDa cell surface type I-membrane glycoprotein with an apparent molecular weight of 44 kDa on SDSPAGE. Fas is a member of the tumor necrosis factor receptor (TNFR) family, which includes TNFR1, TNFR2, CD27, CD30 and CD40. Binding of Fas-ligand (FasL) to Fas or crosslinking of Fas by anti-Fas monoclonal antibodies leads to apoptosis of Fas expressing cells. Both Fas and TNFR contain a 70 amino acids cytoplasmic .death domain. that is responsible for transmitting signal for apoptosis. Apoptosis induced by Fas-Fas ligand interaction is inhibited by a number of cytosolic factors such as the ICE/CED3 family inhibitor CrmA, and the short and long form of FLIP. Insertion of an early transposable element in intron 2 of Fas structural gene, as in the mouse lpr mutations, causes lymphoproliferation and autoimmunity in mutant mice, suggesting that Fas is involved in clonal deletion of autoreactive T cells.

back

Tumor Necrosis Factor Receptor 1 & 2

Tumor necrosis factor receptor 1 and 2 (TNF-R1 and TNF-R2), are 55 and 75 kDa members of a family cell surface molecules including nerve growth factor receptor, Fas/Apo-1, CD30, Ox40 and 4-1BB, which are characterized by cysteine rich motifs in the extracellular domain. While TNF-R1 and TNF-R2 share 28% sequence identity in their extracellular domains, their intracellular domains lack sequence homology which suggests that they differ in their internal signal transduction pathways. TNF-R1 initiates the majority of TNF.s activities, which includes triggering apoptosis of certain tumor cells, mediating the inflammatory response and regulating immune function (Chen). Each pathway is characterized by TNF-induced formation of a multi-protein signaling complex at the cell membrane. TNF and TNF-R1 binding initiates a series of intracellular events that result in activation of the transcription factors NF kappa B and c-Jun. TNF and TNF-R1 binding triggers release of the 80 residue inhibitory protein silencer of death domains (SODD) from the C-terminal intracellular domain of TNF-R1. This domain interacts with TNF receptor-associated death domain (TRADD) which in turn recruits receptor-interacting protein (RIP) TNF-R-associated factor 2 (TRAF2) and Fas-associated death domain (FADD). These three proteins recruit enzymes responsible for initiating signaling events. For example, interaction of SODD with TRADD, and subsequent interactions with FADD initiates Caspase-8 mediated apoptosis. TRAF2 links TNF-R1 with stress activated protein kinase (SAPK) and p38 mitogen activated protein kinases via germinal center kinase (GCK) and receptor interacting protein (RIP). The cytoplasmic domain of TNF-R1 can directly interact with Jak kinases, thereby.

back

© 2004-2010 Acris Antibodies   -   All rights reserved   -   Imprint