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Dynamic protein–protein interactions are involved in most physiological processes and, in particular, for the formation of multiprotein signaling complexes at transmembrane receptors, adapter proteins and effector mole-cules. Because the unregulated induction of signaling complexes has sub-stantial clinical relevance, the investigation of these complexes is an active area of research. | iFEBS Journal MINIREVIEW Examining multiprotein signaling complexes from all angles The use of complementary techniques to characterize complex formation at the adapter protein linker for activation of T cells Jon C. D. Houtman Mira Barda-Saad and Lawrence E. Samelson Laboratory of Cellular and Molecular Biology NationalCancer Institute National institutes of Health Bethesda MD USA Keywords LAT multiprotein complexes signal transduction T cells T cell receptor Correspondence L. E. Samelson Laboratory of Cellular and Molecular Biology NationalCancer Institute National institutes of Health Bethesda MD 20892 USA Fax 1 301 496 8479 Tel 1 301 496 9683 E-mail samelson@helix.nih.gov Received 27 May 2005 revised 10 August 2005 accepted 12 August 2005 doi 10.1111 j.1742-4658.2005.04972.x Dynamic protein-protein interactions are involved in most physiological processes and in particular for the formation of multiprotein signaling complexes at transmembrane receptors adapter proteins and effector molecules. Because the unregulated induction of signaling complexes has substantial clinical relevance the investigation of these complexes is an active area of research. These studies strive to answer questions about the composition and function of multiprotein signaling complexes along with the molecular mechanisms of their formation. In this review the adapter protein linker for activation of T cells LAT will be employed as a model to exemplify how signaling complexes are characterized using a range of techniques. The intensive investigation of LAT highlights how the systematic use of complementary techniques leads to an integrated understanding of the formation composition and function of multiprotein signaling complexes that occur at receptors adapter proteins and effector molecules. Reversible protein-protein interactions are a characteristic of most biochemical pathways. One process dependent on dynamic protein-protein interactions is the formation of multiprotein signaling .