Identification and Characterization of Proteins Involved in Integrin Signaling.

The process of metastasis and invasion of tumor cells requires that the cells regulate their ability to adhere to the surrounding extracellular matrix. Integrins, the family of cell adhesion receptors that mediate the adhesion of cells to the matrix are able to modulate their affinity for ligand. We have identified CD98 as a regulator of integrin affinity using an expression cloning strategy that utilizes the overexpression of free integrin Beta1 cytoplasmic domains. Cells expressing high levels of free Beta1 tails show reduced integrin affinity which results in an inhibition of cell adhesion, cell migration and fibronectin matrix assembly. Proteins involved in integrin affinity regulation were identified by their capacity to complement integrin suppression caused by overexpression of free Beta1 tails. In this report we investigate the mechanisms by which CD98 may affect integrin function.