Several serine/threonine protein kinases have been implicated as intermediates in signal transduction pathways. These include ERK/MAP kinases, ribosomal S6 kinase (Rsk) and Raf-1. Raf-1 is a 74 kDa protein with intrinsic kinase activity towards serine/threonine residues and that is widely expressed in many tissue types and cell lines. Raf-1 activation is dependent on the small molecular weight GTPase Ras, but the means by which this activation occurs is poorly understood. Two proteins putatively involved in this process are Ksr-1 and Tak1. Ksr-1 (kinase suppressor of Ras) is a novel Raf-related protein kinase whose function is required for Ras signal transduction. Whether Ksr-1 lies directly downstream of Ras or acts in a parallel pathway is not yet known. Tak1 (TGFβ-activated kinase) has been shown to participate in the activation of the MAP kinase family in response to TGF? stimulation.