| Modification Notes |
The Dbl family act as guanine nucleotide exchange factors (GEFs) specific for Rho guanosine triphosphatases (GTPases) (1,2). They regulate Rho GTPase function by stimulating formation of the active, GTP-bound state. All Dbl family members invariably possess a tandem domain structure, which consists of a Dbl homology (DH) catalytic domain followed by a pleckstrin homology (PH) regulatory domain (1-3). Dbs (for Dbl’s big sister), also known as Ost or MCF2L, differs from Dbl by the addition of an amino terminal extension and a carboxy terminal SH3 domain (4). Unlike Dbl, it also requires the presence of the PH domain for the intrinsic catalytic activity of the DH domain (1-3). The expression of Dbs is high in several tissues, including brain, and low in thymus and spleen (4). Dbs exhibits guanine nucleotide exchange activity for Rho A and Cdc42 to mediate growth deregulation (2,3,5). Dbs activity involves multiple signaling pathways that include activation of the Elk-1, Jun, and NFkB transcription factors and stimulation of transcription from the cyclin D1 promoter (5). |