Integral receptors function not only as adhesive molecules but can also serve as signal transduction receptors in a variety of cell types. In the H9 T cell line, triggering of the cx4βl(VLA-4) integrin by mAbs against the α4 or βl subunit results in the tyrosine phosphorylation of a 1 OSkD protein (p 105). A chimeric receptor consisting of the extracellular and transmembrane domains of the CD2 antigen and the cytoplasmic domain of the βl integrin subunit -was expressed in H9 cells. Crosslinking of the chimeric CD2/βl construct with CDS-specific mAbs results in a 2-3 fold increase in p105 tyrosine phosphorylation. In contrast, transfectants expressing a truncated form of this receptor failed to show any change in p 105 tyrosine phosphorylation after chimera crosslinking. These results demonstrate that the βl cytoplasmic domain is necessary and sufficient for integrin-mediated tyrosine phosphorylation of p 105 in H9 T cells. Anti-a4 mAb crosslinking of the myelomonocytic cell line HL60 fails to induce tyrosine phosphorylation, but does lead to an increase in MAP kinase (MAPK) activity. However, crosslinking with two different anti-βl mAbs does not induce increased MAPK activity. These results illustrate: 1) cell-specific differences in βl integrin-mediated signaling; and 2) potential differences in the contribution of integrin a and βsubunits to specific signaling cascades.
|Original language||English (US)|
|State||Published - Dec 1 1996|