THE DISCOIDIN DOMAIN RECEPTOR TYROSINE KINASES ARE ACTIVATED BY COLLAGEN

Two mammalian receptor tyrosine kinases (DDR1 and DDR2) have extracell ular domains closely related to a D. discoideum lectin, discoidin, req uired for cell aggregation. Here, we show that the mammalian DDR recep tors bind and are activated by specific types of collagen. Stimulation of DDR receptor tyrosine kinase activity requires the native triple-h elical structure of collagen and occurs over an extended period of tim e. Collagen activation of DDR1 induces phosphorylation of a docking si te for the Shc phosphotyrosine binding domain, whose presence is contr olled by alternative splicing. Activation of DDR2 by collagen results in the up-regulation of matrix metalloproteinase-l expression. These r esults suggest that the discoidin-related DDR tyrosine kinases are nov el collagen receptors with the potential to control cellular responses to the extracellular matrix.