Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins.
Journal:
Science 2003 SepAuthors:
Kim M, Carman CV, Springer TA
Abstract
Although critical for development, immunity, wound healing, and metastasis, integrins represent one of the few classes of plasma membrane receptors for which the basic signaling mechanism remains a mystery. We investigated cytoplasmic conformational changes in the integrin LFA-1 (alphaLbeta2) in living cells by measuring fluorescence resonance energy transfer between cyan fluorescent protein-fused and yellow fluorescent protein-fused alphaL and beta2 cytoplasmic domains. In the resting state the
...[more]se domains were close to each other, but underwent significant spatial separation upon either intracellular activation of integrin adhesiveness (inside-out signaling) or ligand binding (outside-in signaling). Thus, bidirectional integrin signaling is accomplished by coupling extracellular conformational changes to an unclasping and separation of the alpha and beta cytoplasmic domains, a distinctive mechanism for transmitting information across the plasma membrane.[less]
Mesh Headings:
Antibodies, Monoclonal, Antigens, CD11a, Antigens, CD18, Bacterial Proteins, Cell Adhesion, Cell Membrane, Chemokine CXCL12, Chemokines, CXC, Cytoplasm, Dimerization, Fluorescence Resonance Energy Transfer, Green Fluorescent Proteins, Humans, Intercellular Adhesion Molecule-1, Ligands, Luminescent Proteins, Lymphocyte Function-Associated Antigen-1, Protein Conformation, Protein Structure, Tertiary, Receptors, CXCR4, Recombinant Fusion Proteins, Signal Transduction, Talin, Transfection, Tumor Cells, Cultured