The Human WD Repeat Protein WAIT-1 Specifically Interacts with the Cytoplasmic Tails of β7-Integrins*
- From the ‡Institute of Medical Microbiology, Immunology, and Hygiene, Technische Universität, Trogerstrasse 4a, D-81675 München, Germany, and the§Laboratorium für Molekulare Biologie, Genzentrum der Universität München, D-81375 München, Germany
Abstract
Integrins of the β7 subfamily, α4β7 and αEβ7, contribute to lymphocyte homing and to the development of protective or autoreactive immune responses at mucosal sites. The β subunits of integrins are considered important for regulation of stimulated cell adhesion and adhesion-dependent signal transduction. Using a yeast interaction trap screen, a human WD repeat protein, termed WAIT-1, was isolated that interacts with the integrin β7 cytoplasmic tail and is homologous to mouse EED andDrosophila ESC proteins. WAIT-1 also binds to the cytoplasmic domains of α4 and αE but not to those of integrin β1, β2, and αL subunits. Association of WAIT-1 and β7-integrin was confirmed by coprecipitation from transiently transfected 293 cells. The binding site for WAIT-1 was mapped to a short membrane-proximal region of the β7 cytoplasmic tail with Tyr-735 being of critical importance. Northern blot analysis revealed multiple WAIT-1-related transcripts with differential expression in circulating leukocytes, tissue-resident cells of diverse origin, and lymphoid malignancies. These results suggest that WAIT-1, together with the recently identified RACK1, may define a novel subfamily of WD repeat proteins that interact with distinct subsets of integrin cytoplasmic tails and may act as specific regulators of integrin function.
Footnotes
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↵* This work was supported by Wilhelm Sander-Stiftung Grant 95.027.2.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ To whom correspondence should be addressed. Tel.: 49-89-4140-2033; Fax: 49-89-4140-4868; E-mail: holzmannchir{at}med.tu-muenchen.de.
- Abbreviations:
- PCR
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polymerase chain reaction
- RACE
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rapid amplification of cDNA ends
- GST
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glutathione S-transferase
- kb
-
kilobase(s).
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- Received April 15, 1998.
- Revision received July 23, 1998.
