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Regulation of α4 Integrin Avidity in Human B Cells: Requirement for Dephosphorylation Events for High Avidity VCAM‐1 Binding
Author(s) -
Hedman H.,
Lundgren E.
Publication year - 1996
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1996.d01-305.x
Subject(s) - avidity , dephosphorylation , vcam 1 , chemistry , integrin , microbiology and biotechnology , immunology , phosphorylation , biology , biochemistry , antibody , receptor , cell adhesion , cell , phosphatase
The authors compared the phosphorylation‐dependent signal transduction pathways involved in the regulation of adhesiveness of integrin LFA‐1 with that of α4 integrins binding to VCAM‐1. The authors developed an in vitro method to monitor changes in adhesiveness using a VCAM‐1 fusion protein coupled to magnetic beads. For LFA‐1, a similar method has previously been established using an ICAM‐1 fusion protein. Binding of cells was monitored and found to be strictly integrin α4 and VCAM‐1 dependent. The serine/threonine phosphatase inhibitors okadaic acid and calyculin A were equally potent in inhibiting binding to VCAM‐1 as to ICAM‐1, and inhibition of protein phosphatase‐1 (PP1) is proposed to be the important denominator. Similarly, the phorbol ester PDBu, potentially stimulating protein phosphatase‐1 and staurosporine, an inhibitor of serine/threonine kinases, enhanced adhesion to VCAM‐1 as has previously been shown for ICAM‐1. A major difference was that a significant portion of the binding to VCAM‐1 was not susceptible to inhibition by drugs while binding to ICAM‐1 could be completely inhibited. We propose that the adhesiveness of the α4 integrins for VCAM‐1 and of LFA‐1 for ICAM‐1 is regulated by similar or identical protein kinases and phosphatases.