Receptor signaling complexes

Dimerization allows the kinase activity of both intracellular chains to encounter target sequences on the other, linked receptor molecule. This enables the intermolecular cross-phosphorylation of several tyrosine residues (Figure 8.2). The phosphorylated dimer then constitutes the active receptor. It possesses an array of phosphotyrosines that enable it to bind proteins to form receptor signaling complexes. Additionally, the dimerized and phosphorylated receptor has the potential of phospho-rylating its targets. 

Src and PTB Homology Domains and the Formation of Receptor Signaling Complexes... 

A number of signal-transduction pathways branch out from the receptor signaling complex. Five such branches are described in the following text (see Figure 8.4). 

Ettenbeeg, S. a., et al., Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex. J Biol Chem, 2001, 276(29), 27677-84. 

Takesono A, Nowak MW, Cismowski M, Duzic E, Lanier SM (2002) Activator of G-protein signaUng 1 blocks GIRK channel activation by a G-protein-coupled receptor apparent disruption of receptor signaling complexes. J Biol Chem 277 13827-13830... 

Kim M, Jiang LH, Wilson HL, North RA, Surprenant A. Proteomic and functional evidence for a P2X7 receptor signalling complex. EMBO J 2001 20 6347-6358. 

Kreienkamp HJ. Organisation of G protein-coupled receptor signalling complexes by scaffolding proteins. Curr Opin Pharmacol 2002 2 581-586. 

Randal, M., and Kossiakoff, A. A. (2001). The structure and activity of a monomeric interferon-gamma alpha-chain receptor signaling complex. Structure (Camb) 9(2), 155-163. 

ASSEMBLY OF POST-RECEPTOR SIGNALING COMPLEXES FOR THE TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY... 

While the current structural and functional studies have shed lights on the molecular mechanisms of post-receptor signal transduction by the TNFR superfamUy, many important questions remain. One such question is the structural basis for the formation of death receptor signaling complexes, involving DD-DD and DED-DED interactions. Another question is the molecular basis of TRAP downstream signaling. Does it involve oligomerization and proximity induced activation of down-stream effectors, or conformational modulations Because of the importance of the TNFR superfamily in human disease, an ultimate question lies on the translation of structural and functional studies into therapeutic applications. 

VanArsdale, T. L., VanArsdale, S. L., Force, W. R., Walter, B. N., Mosialos, G., Kieff, E., Reed, J. C., and Ware, C. F. (1997). Lymphotoxin-/ receptor signaling complex Role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor kB. PNAS 94, 2460-2465. 

Davare MA, Avdonin V, Hall DD, et al. A p2 adrenergic receptor signaling complex assembled with the Ca2+ channel Ca(v)1.2. Science 2001 293 98-101. 

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Chow, D., He, X., Snow, A. L., Rosejohn, S., and Garcia, K. C. (2001a). Structure of an extracellular gplSO cytokine receptor signaling complex. Science 291, 2150-2155. 

Assembly of Post-Receptor Signaling Complexes for the Tumor Necrosis Factor Receptor Supetfamily... 

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Hartc MT, Haga IR, Maloney G et al. The poxvirus protein A52R uigets Toll-like receptor signaling complexes to suppress host defense. J Exp Med 2003 I97(3) 343-351. 

Maudsley S, Martin B, Luttrell LM. G protein-coupled receptor signaling complexity in neuronal tissue implications for novel therapeutics. Curr Alzheimer Res. 2007 4(1) 3-19. 

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