Activated conformations of very late activation integrins detected by a group of antibodies (HUTS) specific for a novel regulatory region (355-425) of the common β1 chain

Alfonso Luque, Manuel Gómez, Wilma Puzon, Yoshikazu Takada, Francisco Sánchez-Madrid, Carlos Cabañas

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

The very late activation antigens (VLA) or β1 integrins mediate cell attachment to different extracellular matrix proteins and intercellular adhesions. The ligand binding activity of these adhesion receptors is not constitutive and can be regulated by temperature, presence of extracellular divalent cations, stimulatory monoclonal antibodies (mAbs), and cellular activation. We have generated three novel mAbs, HUTS-4, HUTS-7, and HUTS-21, recognizing specific epitopes on the common β1 subunit (CD29) of VLA integrins whose expression correlates with the ligand binding activity of these heterodimeric glycoproteins. This correlation has been demonstrated for several integrin heterodimers in different cell systems using a variety of extracellular and intracellular stimuli for integrin activation. Thus, the presence of micromolar concentrations of extracellular Mn2+, preincubation with the activating anti-β1 mAb TS2/16, and cell treatment with phorbol esters or calcium ionophores, induced the expression of the HUTS β1 epitopes on T lymphoblasts. Using a panel of human-mouse β1 chimeric molecules, we have mapped these epitopes to the 355-425 sequence of the β1 polypeptide. This segment represents therefore a novel regulatory region of β1 that is exposed upon integrin activation. Interestingly, binding of HUTS mAbs to partially activated VLA integrins results in maximal activation of these adhesion receptors and enhancement of cell adhesion to β1 integrin ligands collagen, laminin, and fibronectin.

Original languageEnglish
Pages (from-to)11067-11075
Number of pages9
JournalJournal of Biological Chemistry
Volume271
Issue number19
DOIs
Publication statusPublished - 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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