Figure EV5. Illustration of direct and indirect MAPK substrates.

Most of the D‐motif‐containing proteins likely fall into two categories. In proteins that are direct MAPK substrates (upper diagram), the docking motif might serve to enhance phosphorylation of regulatory sites. This is exemplified by a known substrate, GAB1 (with the target motif being only recently identified) (Wolf et al, 2015). Other proteins can act as scaffolds to aid phosphorylation of substrates without docking motifs (here termed indirect MAPK substrates, lower diagram). For example, the requirement for APBA2 to mediate JNK‐dependent phosphorylation of beta‐amyloid precursor protein (β‐APP) has already been described and the minimally required fragment of APBA2 contains the JIP1‐type docking motif‐containing region as well as a PTB domain (Taru & Suzuki, 2004).