Integrin receptors can mediate transmembrane signaling in response to ligand binding. To further examine the role of the integrin subunit in these signaling functions, we assessed the contribution of the 6 cytoplasmic domain variants to the signaling properties of the 61 integrin using P388D1 cells that had been transfected with either the 6A or the 6B cDNA. The 6A1 and 6B1 receptors induced marked quantitative differences in the tyrosine phosphorylation of several proteins after binding to laminin. Specifically, the 6A cytoplasmic domain was more effective than the 6B cytoplasmic domain in inducing the tyrosine phosphorylation of three major proteins (molecular mass, 120, 110, and 76 kDa). In addition to these proteins, we also observed that the tyrosine phosphorylation of the cytoskeletal protein paxillin was increased significantly more by 6A1 integrin-mediated adhesion to laminin than by that of 6B1. This differential pattern of tyrosine phosphorylation induction does not appear to be a secondary event initiated by cell shape changes. Also, differences in tyrosine phosphorylation in the 6 transfectants were not evident in response to attachment to other substrates. These findings provide biochemical evidence for functional differences between subunit cytoplasmic domain variants of the same integrin.

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