Class- and splice variant-specific association of CD98 with integrin beta cytoplasmic domains.

CD98 is a type II transmembrane protein involved in neutral and basic amino acid transport and in cell fusion events. CD98 was implicated in the function of integrin adhesion receptors by its capacity to reverse suppression of integrin activation by isolated integrin beta(1A) domains. Here we report that CD98 associates with integrin beta cytoplasmic domains with a unique integrin class and splice variant specificity. In particular, CD98 interacted with the ubiquitous beta(1A) but not the muscle-specific splice variant, beta(1D), or leukocyte-specific beta(7) cytoplasmic domains. The ability of CD98 to associate with integrin cytoplasmic domains correlated with its capacity to reverse suppression of integrin activation. The association of CD98 with integrin beta(1A) cytoplasmic domains may regulate the function and localization of these membrane proteins.