Fig. 7: Proposed model of MAP4K4 and STRN3 regulation of cell migration and proliferation in MB.
From: Cooperation of Striatin 3 and MAP4K4 promotes growth and tissue invasion
MAP4K4 is activated downstream of RTK signaling and exerts both pro-invasive and anti-proliferative activities in MB cells. Invasion regulation: STRN3 cooperates with MAP4K4 to control cell migration, invasion, and actin cytoskeleton remodeling, independently from PP2A activity. This cooperation of MAP4K4 and STRN3 is necessary for the FGFR-induced activation of motility-associated effectors nPKCs and VASP. Proliferation regulation: MAP4K4 causes LATS1/2 phosphorylation, which promotes the activation of the Hippo pathway. Hippo pathway activation results in the phosphorylation and degradation of the transcriptional regulator YAP. The consequent repression of YAP transcriptional activity leads to a proliferation arrest. STRN3 promotes PP2A-mediated inactivation of MAP4K4 function toward Hippo activation, resulting in an increase of YAP transcriptional activity and cell proliferation.
