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J Biol Chem. 2005 Sep 30;280(39):33200-5. Epub 2005 Jul 28.

AF6 negatively regulates Rap1-induced cell adhesion.

Author information

1
Department of Physiological Chemistry and Centre of Biomedical Genetics, University Medical Centre, Utrecht 3508 AB, The Netherlands.

Abstract

AF6 is involved in the connection of membrane-associated proteins to the actin cytoskeleton. It binds to Ras-like small GTPases and is suggested to be an effector of both Ras and Rap. Here we show that knockdown of AF6 in T cells by RNA interference enhanced Rap1-induced integrin-mediated cell adhesion, whereas overexpression of AF6 had the opposite effect. Interestingly, AF6-induced inhibition of cell adhesion correlated with an increase in RapGTP levels. Like AF6, protein KIAA1849 contains a Ras association domain and interacted with Rap1. However, KIAA1849 did not inhibit Rap1-induced cell adhesion. We concluded that AF6 is a negative regulator of Rap-induced cell adhesion. We proposed that AF6 inhibits Rap-mediated cell adhesion by sequestering RapGTP in an unproductive complex and thus prevents the interaction of Rap1 not only with effectors that mediate adhesion but also with Rap GTPase-activating proteins. Thus, AF6 may buffer RapGTP in resting T cells and maintain them in a non-adherent state.

PMID:
16051602
DOI:
10.1074/jbc.M505057200
[Indexed for MEDLINE]
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