RAF regulation is highly complex and is not solely mediated by conformational changes but also requires phosphorylation. Several phosphorylation sites on RAF1 have been identified that are involved in its kinase activity. Two of these phosphorylation sites are serine 338 (S338) and tyrosine 340 and 341 (Y340/341). Gringhuis et al. demonstrated that ManLAM activation of CD209 (DC-SIGN) results in induced phosphorylation of RAF1 on S338 and Y340/341. The phosphorylation of S338 is mediated by p21-activated kinases (PAK). Inhibition of Rho GTPases with toxin B blocks CD209 induced phosphorylation of RAF1on S338 (Gringhuis et al. 2007, Wellbrock et al. 2004).