Critical cysteine residues for regulation of integrin αIIbβ3 are clustered in the epidermal growth factor domains of the β3 subunit

Tetsuji Kamata, Hironobu Ambo, Wilma Puzon-McLaughlin, Kenneth Khiem Tieu, Makoto Handa, Yasuo Ikeda, Yoshikazu Takada

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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 β3 subunit are involved in the regulation of αIIbβ3. In the present study, we studied systematically the role of disulphide bonds in β3 on the ligand-binding function of αIIbβ3 by mutating individual cysteine residues of β3 to serine. We found that the disulphide bonds that are critical for αIIbβ3 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 αIIbβ3 fully. In contrast, only two (of 13) disulphide bonds tested outside the EGF domains activated αIIbβ3. These results suggest that the disulphide bonds in the EGF domains should be intact to keep αIIbβ3 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.

Original languageEnglish
Pages (from-to)1079-1082
Number of pages4
JournalBiochemical Journal
Volume378
Issue number3
DOIs
Publication statusPublished - Mar 15 2004
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Integrins
Cysteine
Disulfides
Protein Disulfide-Isomerases
Reducing Agents
Serine
Ligands
Oxidation

Keywords

  • αIIβ3 integrin
  • Disulphide bond
  • Epidermal growth factor domain (EGF domain)
  • Fibrinogen
  • Integrin activation
  • Mutagenesis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Critical cysteine residues for regulation of integrin αIIbβ3 are clustered in the epidermal growth factor domains of the β3 subunit. / Kamata, Tetsuji; Ambo, Hironobu; Puzon-McLaughlin, Wilma; Tieu, Kenneth Khiem; Handa, Makoto; Ikeda, Yasuo; Takada, Yoshikazu.

In: Biochemical Journal, Vol. 378, No. 3, 15.03.2004, p. 1079-1082.

Research output: Contribution to journalArticle

Kamata, T, Ambo, H, Puzon-McLaughlin, W, Tieu, KK, Handa, M, Ikeda, Y & Takada, Y 2004, 'Critical cysteine residues for regulation of integrin αIIbβ3 are clustered in the epidermal growth factor domains of the β3 subunit', Biochemical Journal, vol. 378, no. 3, pp. 1079-1082. https://doi.org/10.1042/BJ20031701
Kamata, Tetsuji ; Ambo, Hironobu ; Puzon-McLaughlin, Wilma ; Tieu, Kenneth Khiem ; Handa, Makoto ; Ikeda, Yasuo ; Takada, Yoshikazu. / Critical cysteine residues for regulation of integrin αIIbβ3 are clustered in the epidermal growth factor domains of the β3 subunit. In: Biochemical Journal. 2004 ; Vol. 378, No. 3. pp. 1079-1082.
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