Regulation of Tiam1-Rac signalling.

The GTPases of the Rho family are molecular switches that play an important role in a wide range of cellular processes and are increasingly implicated in tumourigenesis. Unlike what was found for the Ras oncogenes in tumours, hardly any activating mutations have been found in the genes encoding Rho proteins. In the past, we have identified Tiam1 (T-lymphoma invasion and metastasis) as a specific activator for the Rho-like GTPase Rac. In vivo, Tiam1 deficiency protects against Ras-induced skin carcinogenesis, underscoring the consequences of deregulated signalling for the onset and progression of tumours. Thus, an important level of regulation of signalling via the Rho-like GTPases comes from the specific control of their activators. In this paper, we review what is known on the specific regulation of Tiam1 signalling towards Rac.