Tests of integrin transmembrane domain homo-oligomerization during integrin ligand binding and signaling. J Biol Chem 2011 Jan 21;286(3):1860-7
Date
11/18/2010Pubmed ID
21081497Pubmed Central ID
PMC3023481DOI
10.1074/jbc.M110.193797Scopus ID
2-s2.0-78751526817 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Integrin transmembrane (TM) and/or cytoplasmic domains play a critical role in integrin bidirectional signaling. Although it has been shown that TM and/or cytoplasmic α and β domains associate in the resting state and separation of these domains is required for both inside-out and outside-in signaling, the role of TM homomeric association remains elusive. Formation of TM homo-oligomers was observed in micelles and bacterial membranes previously, and it has been proposed that homomeric association is important for integrin activation and clustering. This study addresses whether integrin TM domains form homo-oligomers in mammalian cell membranes using cysteine scanning mutagenesis. Our results show that TM homomeric interaction does not occur before or after soluble ligand binding or during inside-out activation. In addition, even though the cysteine mutants and the heterodimeric disulfide-bounded mutant could form clusters after adhering to immobilized ligand, the integrin TM domains do not form homo-oligomers, suggesting that integrin TM homomeric association is not critical for integrin clustering or outside-in signaling. Therefore, integrin TM homo-oligomerization is not required for integrin activation, ligand binding, or signaling.
Author List
Wang W, Zhu J, Springer TA, Luo BHAuthor
Jieqing Zhu PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SubstitutionCell Adhesion
Cell Line
Humans
Integrins
Ligands
Mutagenesis
Protein Binding
Protein Multimerization
Protein Structure, Tertiary
Signal Transduction
