PROTEIN-KINASE MEDIATORS OF INTEGRIN SIGNAL-TRANSDUCTION

Protein kinases are important mediators of signal transduction initiat ed by soluble growth factors and cytokines. Cellular interactions with the extracellular matrix are mediated largely by members of the integ rin class of cell adhesion molecules, which also subsume signal transd uction functions required for cell growth, differentiation, and surviv al. Here we review the involvement of protein kinases in mediating int egrin intracellular signal transduction and the possible role for thes e molecules in regulating integrin adhesion. Although in most cases me chanistic details are incomplete, the emerging theme of protein kinase s mediating cross-talk between growth factor receptor and integrin sig nalling systems provides a timely backdrop against which to present ne w developments in this area. The contribution of the actin cytoskeleto n to integrin signal transduction is discussed, with respect to the co ncept of 'solid-state' signalling providing a mechanism for imposing o rder on the protein-protein interactions which underlie signal discrim ination. Moreover, we review evidence that dysregulated integrin signa lling contributes to pathological processes including arthritis, throm basthenia, leucocyte adhesion deficiencies, and tumour angiogenesis an d invasion.