An activated Ras protein alters cell adhesion by dephosphorylating Dictyostelium DdCAD-1.

RasG-regulated signal transduction has been linked to a variety of growth-specific processes and appears to also play a role in the early development of Dictyostelium discoideum. In an attempt to uncover some of the molecular components involved in Ras-mediated signalling, several proteins have been described previously, including the cell adhesion molecule DdCAD-1, whose phosphorylation state was affected by the expression of the constitutively activated RasG, RasG(G12T). Here it has been shown that a cadA null strain lacks the phosphoproteins that were tentatively identified as DdCAD-1, confirming its previous designation. Further investigation revealed that cells expressing RasG(G12T) exhibited increased cell-cell cohesion, concomitant with reduced levels of DdCAD-1 phosphorylation. This increased cohesion was DdCAD-1-dependent and was correlated with increased localization of DdCAD-1 at the cell surface. DdCAD-1 phosphorylation was also found to decrease during Dictyostelium aggregation. These results revealed a possible role for protein phosphorylation in regulating DdCAD-1-mediated cell adhesion during early development. In addition, the levels of DdCAD-1 protein were substantially reduced in a rasG null cell line. These results indicate that RasG affects both the expression and dephosphorylation of DdCAD-1 during early development.