BETA(1) INTEGRINS SIGNAL LIPID 2ND-MESSENGERS REQUIRED DURING CELL-ADHESION

Clustering of integrin receptors during cell adhesion stimulates signa l transduction across the cell membrane. Second messengers are generat ed, activating cytosolic proteins and causing cytoskeletal assembly an d rearrangement. HeLa cell adhesion to a collagen substrate has been s hown to initiate an arachidonic acid-mediated signaling pathway, leadi ng to the activation of protein kinase C (PKC) and cell spreading. To determine the role of integrin receptors in triggering this signaling pathway, monoclonal antibodies to beta(1) integrins were used to eithe r cluster integrins on the cell surface or to provide an integrin-depe ndent substrate for cell adhesion. Using this approach, we have define d a pathway required for cell spreading that can be initiated by the l igation of integrins and leads to the activation of PKC. Specifically, our results indicate that clustering beta(1) integrins results in the activation of phospholipase A, leading to the production of arachidon ic acid and the activation of PKC.