Raf-like Ras/Rap-binding domains in RGS12-and still-life-like signalling proteins

Ras proteins play critical roles in regulating cell growth and differentiat ion, and mutated Ras genes are expressed in a variety of human cancers. Con sequently, much interest has centered on the binding partners of Ras, inclu ding the Ras-binding domain (RBD) of Raf kinase. Here evidence is presented that domains homologous to the Raf RED are present in tandem in RGS12, RGS 14 and LOGO, and singly in molecules similar to mouse Tiam-1. In addition; RGS12, RGS14 and LOCO are shown to contain single "LGN motifs" that are gua nine nucleotide exchange factors specific for the cc-subunit of G proteins. These findings indicate "cross-talk" interactions between signalling pathw ays involving Ras and Rap and pathways involving Rho, Rac and Ga GTPases.