Identification of a regulatory region of integrin β1 subunit using activating and inhibiting antibodies

Yoshikazu Takada, Wilma Puzon

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Members of the β1 integrin subfamily recognize multiple ligands such as fibronectin, laminin, and collagen and mediate cell-cell and cell-extracellular matrix interactions, β1 subunit may play a central role in regulating β1 integrin avidity. Here we have identified a small region of β1 subunit (residues 207-218) that is critical for the binding of both activating (8A2, A1A5, and TS2/16) and inhibiting (4B4, 4B5, 13, AIIB2, and P4C10) monoclonal antibodies against human β1 using interspecies chimeric β1 and site-directed mutagenesis. Chicken β1 that has human sequence within residues 207-218 (CH mutant) is recognized by all the human specific antibodies listed above. The region 207-218 is located between the two putative ligand binding sites (residues 120-182 and 220-231), and the amino acid sequence of the region involves a predicted bend structure. The other anti-β1 antibodies that do not affect cell . attachment to ligands (K20, 102DF5, LM442, and LM534) recognized the carboxyl-terminal regions of extracellular domain of β1 (residues 426-587 for K20 and 588-708 for 102DF5, LM442, and LM534, respectively). Our data suggest a potential mechanism for the avidity regulation of β1 integrin through conformational changes of β1 subunit.

Original languageEnglish (US)
Pages (from-to)17597-17601
Number of pages5
JournalJournal of Biological Chemistry
Volume268
Issue number23
StatePublished - Aug 15 1993
Externally publishedYes

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Nucleic Acid Regulatory Sequences
Integrins
Ligands
Antibodies
Mutagenesis
Laminin
Fibronectins
Collagen
Site-Directed Mutagenesis
Binding Sites
Monoclonal Antibodies
Extracellular Matrix
Amino Acids
Anti-Idiotypic Antibodies
Amino Acid Sequence
Chickens

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of a regulatory region of integrin β1 subunit using activating and inhibiting antibodies. / Takada, Yoshikazu; Puzon, Wilma.

In: Journal of Biological Chemistry, Vol. 268, No. 23, 15.08.1993, p. 17597-17601.

Research output: Contribution to journalArticle

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