Binding specificity of multiprotein signaling complexes is determined by both cooperative interactions and affinity preferences

HOUTMAN JC, HIGASHIMOTO Y, DIMASI N, CHO S, YAMAGUCHI H, BOWDEN B, REGAN C, MALCHIODI EL, MARIUZZA R, SCHUCK P, APPELLA E & SAMELSON LE

BIOCHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2004 vol. 43 p. 4170 - 4178

0006-2960

The generation of multiprotein complexes at receptors and adapter proteins is crucial for the activation of intracellular signaling pathways. In this study, we used multiple biochemical and biophysical methods to examine the binding properties of several SH2 and SH3 domain containing signaling proteins as they interact with the adapter protein Linker for Activation of Tccells (LAT) to form multiprotein complexes. We observed that the binding specificity of these proteins for various LAT tyrosines appears to be constrained both by the affinity of binding and by cooperative protein-protein interactions. These studies provide quantitative information on how different binding parameters can determine in vivo binding site specificity observed for multiprotein signaling complexes.