Fig. 1
From: Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi
Combined MAPK and β-catenin pathway activating mutations define deep penetrating nevi a β-catenin pathway mutations, affecting CTNNB1 or APC, and MAPK pathway mutations co-occur in deep penetrating nevi (DPN). Nevi with overlapping features of DPN and blue nevus harbor GNAQ activating mutations and are genetically distinct. BRAF activating mutations are mutually exclusive with MAP2K1 alterations. b CTNNB1 missense mutations affect codons of a critical domain that is phosphorylated and regulates subsequent ubiquitin-mediated degradation. c Indels of MAP2K1 cluster near a highly conserved lysine within the kinase catalytic domain. One small deletion affects the negative regulatory region (NRR). DD, docking domain for ERK1/2; NES, nuclear export signal; AL, activation loop within the kinase catalytic domain; PRD, proline-rich domain within the kinase catalytic domain; DVD, domain of versatile docking. d. MAP2K1 mutations activate MAP kinase signaling, which could be inhibited by the MEK inhibitor trametinib
