Involvement of transmembrane domain interactions in signal transduction by alpha/beta integrins.
The alpha and beta subunits of alpha/beta heterodimeric integrins function together to bind ligands in the extracellular region and transduce signals across cellular membranes. A possible function for the transmembrane regions in integrin signaling has been proposed from structural and computational data. We have analyzed the capacity of the integrin alpha(2), alpha(IIb), alpha(4), beta(1), beta(3), and beta(7) transmembrane domains to form homodimers and/or heterodimers. Our data suggest that the integrin transmembrane helices can help to stabilize heterodimeric integrins but that the interactions do not specifically associate particular pairs of alpha and beta subunits; rather, the alpha/beta subunit interaction constrains the extramembranous domains, facilitating signal transduction by a promiscuous transmembrane helix-helix association.
Schneider
Dirk
D
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8114, USA.
Engelman
Donald M
DM
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism*; D039641:Integrin beta Chains / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000378:metabolism
D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D016023:Integrins; D001616:beta-Galactosidase