A novel activating anti-β1 integrin monoclonal antibody binds to the cysteine-rich repeats in the β1 chain

Randall J. Faull, Jian Wang, David I. Leavesley, Wilma Puzon, Graeme R. Russ, Dietmar Vestweber, Yoshikazu Takada

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Abstract

The functional status of an integrin depends on the conformation of its extracellular domain, which is controlled by the cell expressing that receptor. The transmission of regulatory signals from within the cell is considered to be via propagated conformational changes from the receptor's cytoplasmic tails to the extracellular ligand binding 'pocket.' The end result is increased accessibility of the ligand binding pocket in the high affinity ('active') form of integrins. We report a novel monoclonal antibody (QE.2E5) that binds within the cysteine-rich repeats in the integrin β1 chain and induces high affinity binding of fibronectin to the integrin α5β1. The QE.2E5 epitope is located approximately 200 residues both from the predicted binding site for fibronectin and from the epitopes recognized by other activating anti-β1 monoclonal antibodies. It is also expressed on β1 integrins from a number of nonhuman species. Although they have the same functional effects, the binding of QE.2E5 and another activating antibody (8A2) to the receptor have contrasting effects on the expression of an activation-dependent epitope in the β1 chain. We propose that the cysteine- rich repeats contain a regulatory region that is distinct from those previously described in the integrin β1 chain.

Original languageEnglish
Pages (from-to)25099-25106
Number of pages8
JournalJournal of Biological Chemistry
Volume271
Issue number41
DOIs
Publication statusPublished - 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Faull, R. J., Wang, J., Leavesley, D. I., Puzon, W., Russ, G. R., Vestweber, D., & Takada, Y. (1996). A novel activating anti-β1 integrin monoclonal antibody binds to the cysteine-rich repeats in the β1 chain. Journal of Biological Chemistry, 271(41), 25099-25106. https://doi.org/10.1074/jbc.271.41.25099