Cross talk between beta(1) and alpha(V) integrins: beta(1) affects beta(3)mRNA stability

There is increasing evidence that a fine-tuned integrin cross talk can gene rate a high degree of specificity in cell adhesion, suggesting that spatial ly and temporally coordinated expression and activation of integrins are mo re important for regulated cell adhesive functions than the intrinsic speci ficity of individual receptors. However, little is known concerning the mol ecular mechanisms of integrin cross talk. With the use of beta (1)-null GD2 5 cells ectopically expressing the beta (1)A integrin subunit, we provide e vidence for the existence of a cross talk between beta (1) and alpha (V) in tegrins that affects the ratio of alpha (V)beta (3) and alpha (V)beta (5) i ntegrin cell surface levels. In particular, we demonstrate that a down-regu lation of alpha (V)beta (3) and an up-regulation of alpha (V)beta (5) occur as a consequence of beta (1)A expression. Moreover, with the use of GD25 c ells expressing the integrin isoforms beta B-1 and beta D-1, as well as two beta (1) cytoplasmic domain deletion mutants lacking either the entire cyt oplasmic domain (beta 1TR) or only its "variable" region (beta 1COM), we sh ow that the effects of beta (1) over av integrins take place irrespective o f the type of beta (1) isoform, but require the presence of the "common" re gion of the beta (1), cytoplasmic domain. In an attempt to establish the re gulatory mechanism(s) whereby beta (1) integrins exert their trans-acting f unctions, we have found that the down-regulation of alpha (V)beta (3) is du e to a decreased beta (3) subunit mRNA stability, whereas the up-regulation of alpha (V)beta (5) is mainly due to translational or posttranslational e vents. These findings provide the first evidence for an integrin cross talk based on the regulation of mRNA stability.