Publication Date:
2003-09-23
Description:
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 these 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Minsoo -- Carman, Christopher V -- Springer, Timothy A -- CA31798/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Sep 19;301(5640):1720-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14500982" target="_blank"〉PubMed〈/a〉
Keywords:
Antibodies, Monoclonal
;
Antigens, CD11a/*chemistry
;
Antigens, CD18/*chemistry
;
Bacterial Proteins
;
Cell Adhesion
;
Cell Membrane/*metabolism
;
Chemokine CXCL12
;
Chemokines, CXC/metabolism
;
Cytoplasm/*chemistry
;
Dimerization
;
Fluorescence Resonance Energy Transfer
;
Green Fluorescent Proteins
;
Humans
;
Intercellular Adhesion Molecule-1/metabolism
;
Ligands
;
Luminescent Proteins
;
Lymphocyte Function-Associated Antigen-1/chemistry/*metabolism
;
Protein Conformation
;
Protein Structure, Tertiary
;
Receptors, CXCR4/metabolism
;
Recombinant Fusion Proteins/chemistry
;
*Signal Transduction
;
Talin/chemistry/metabolism
;
Transfection
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
