title: Binding specificity of multiprotein signaling complexes is determined by both cooperative interactions and affinity preferences.
abstract: 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 T-cells (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.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jon C D
authors.initials: JC
authors.lastname: Houtman
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Higashimoto
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Dimasi
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Cho
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Brent
authors.initials: B
authors.lastname: Bowden
authors.forename: Carole
authors.initials: C
authors.lastname: Regan
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Malchiodi
authors.forename: Roy
authors.initials: R
authors.lastname: Mariuzza
authors.forename: Peter
authors.initials: P
authors.lastname: Schuck
authors.forename: Ettore
authors.initials: E
authors.lastname: Appella
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Samelson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology; D002942:Circular Dichroism; D051380:GRB2 Adaptor Protein; D007424:Intracellular Fluid / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D051966:Phospholipase C gamma; D010748:Phosphopeptides / Q000737:chemistry / Q000502:physiology; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D010738:Type C Phospholipases / Q000737:chemistry / Q000502:physiology; D014443:Tyrosine / Q000737:chemistry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051380:GRB2 Adaptor Protein; C495949:Grb2 protein, mouse; C491734:Lat protein, mouse; D046911:Macromolecular Substances; D008565:Membrane Proteins; C498726:Mona protein, mouse; D010446:Peptide Fragments; D010748:Phosphopeptides; D010750:Phosphoproteins; D011506:Proteins; D011994:Recombinant Proteins; C092947:SLP-76 signal Transducing adaptor proteins; D014443:Tyrosine; D010738:Type C Phospholipases; D051966:Phospholipase C gamma