Journal
BIOCHEMICAL JOURNAL
Volume 378, Issue -, Pages 1079-1082Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20031701
Keywords
alpha II beta 3 integrin; disulphide bond; epidermal growth factor domain (EGF domain); fibrinogen; integrin activation; mutagenesis
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Funding
- NIGMS NIH HHS [GM47157] Funding Source: Medline
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Chemical or enzymic reduction/oxidation of integrin cysteine residues (e.g. by reducing agents and protein disulphide isomerase) may be a mechanism for regulating integrin function. It has also been proposed that unique cysteine residues in the integrin 3 subunit are involved in the regulation of alphaIIbeta3. In the present study, we studied systematically the role of disulphide bonds in 3 on the ligand-binding function of alphaIIbbeta3 by mutating individual cysteine residues of beta3 to serine. We found that the disulphide bonds that are critical for alphaIIbbeta3 regulation are clustered within the EGF (epidermal growth factor) domains. Interestingly, disrupting only a single disulphide bond in the EGF domains was enough to activate alphaIIbeta3 fully. In contrast, only two (of 13) disulphide bonds tested outside the EGF domains activated aIIbbeta3. These results suggest that the disulphide bonds in the EGF domains should be intact to keep alphaIIbbeta3 in an inactive state, and that there is no unique cysteine residue in the EGF domain critical for regulating the receptor. The cysteine residues in the EGF domains are potential targets for chemical or enzymic reduction.
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