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|Title:||The integrin αLβ2 hybrid domain serves as a link for the propagation of activation signal from its stalk regions to the I-like domain||Authors:||Tng, E.
|Issue Date:||24-Dec-2004||Citation:||Tng, E., Tan, S.-M., Ranganathan, S., Cheng, M., Law, S.K.A. (2004-12-24). The integrin αLβ2 hybrid domain serves as a link for the propagation of activation signal from its stalk regions to the I-like domain. Journal of Biological Chemistry 279 (52) : 54334-54339. ScholarBank@NUS Repository.||Abstract:||Integrin activation involves global conformational changes as demonstrated by various functional and structural analyses. The integrin β hybrid domain is proposed to be involved in the propagation of this activation signal. Our previous study showed that the integrin β2-specific monoclonal antibody 7E4 abrogates monoclonal antibody KIM185-activated but not Mg 2+/EGTA-activated leukocyte function-associated antigen-1 (LFA-1; αLβ2)-mediated adhesion to ICAM-1. Here we investigated the allosteric inhibitory property of 7E4. By using human/mouse chimeras and substitution mutations, the epitope of 7E4 was mapped to Val 407, located in the mid-region of the β2 hybrid domain. Two sets of constitutively active LFA-1 variants were used to examine the effect of 7E4 on LFA-1/ICAM-1 binding. 7E4 attenuated the binding of variants that have modifications to regions membrane proximal with respect to the β2 hybrid domain. In contrast, the inhibitory effect was minimal on variants with alterations in the αLI- and β2 I-like domains preceding the hybrid domain. Furthermore, 7E4 abrogated LFA-1/ICAM-1 adhesion of phorbol 12-myristate 13-acetate-treated MOLT-4 cells. Our data demonstrate that interaction between the hybrid and I-like domain is critical for the regulation of LFA-1-mediated adhesion.||Source Title:||Journal of Biological Chemistry||URI:||http://scholarbank.nus.edu.sg/handle/10635/113680||ISSN:||00219258|
|Appears in Collections:||Staff Publications|
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