Cross Talk between β(1) and α(V) Integrins: β(1) Affects β(3) mRNA Stability

There is increasing evidence that a fine-tuned integrin cross talk can generate a high degree of specificity in cell adhesion, suggesting that spatially and temporally coordinated expression and activation of integrins are more important for regulated cell adhesive functions than the intrinsic specificity of individual receptors. However, little is known concerning the molecular mechanisms of integrin cross talk. With the use of β(1)-null GD25 cells ectopically expressing the β(1)A integrin subunit, we provide evidence for the existence of a cross talk between β(1) and α(V) integrins that affects the ratio of α(V)β(3) and α(V)β(5) integrin cell surface levels. In particular, we demonstrate that a down-regulation of α(V)β(3) and an up-regulation of α(V)β(5) occur as a consequence of β(1)A expression. Moreover, with the use of GD25 cells expressing the integrin isoforms β(1)B and β(1)D, as well as two β(1) cytoplasmic domain deletion mutants lacking either the entire cytoplasmic domain (β(1)TR) or only its “variable” region (β(1)COM), we show that the effects of β(1) over α(V) integrins take place irrespective of the type of β(1) isoform, but require the presence of the “common” region of the β(1) cytoplasmic domain. In an attempt to establish the regulatory mechanism(s) whereby β(1) integrins exert their trans-acting functions, we have found that the down-regulation of α(V)β(3) is due to a decreased β(3) subunit mRNA stability, whereas the up-regulation of α(V)β(5) is mainly due to translational or posttranslational events. These findings provide the first evidence for an integrin cross talk based on the regulation of mRNA stability.