Meta-Biol

• Pathways

KRAS4B is phosphorylated on serine 181 by PKC theta or cGMP dependent protein kinase 2 (PRKG2) (Bivona et al, 2006; Alvarez-Moya et al, 2010; Cho et al, 2016; reviewed in Ahearn et al, 2018). Serine 181 lies in a polybasic region unique to KRAS upstream of the CaaX motif. Phosphorylation at this position decreases the affinity of KRAS4B for the membrane and promotes internalization (Bivona et al, 2006; Barcelo et al, 2013; Jang et al, 2015). S181 phosphorylation has been shown to restrict cellular proliferation and oncogenesis in part by promoting BCL2L (also known as BCL-XL)-dependent apoptosis (Bivona et al, 2006; Mohammad et al, 1998; Kollar et al, 2014). Phosphorylation at S181 may also interfere with the binding of calmodulin to KRAS4B, thus disrupting calmodulin-dependent supression of signaling downstream of RAS (Wang et al, 2001; Villalonga et al, 2001).