TY - JOUR AU - Hadad, Miriam AU - Aviram, Sharon AU - Darlyuk-Saadon, Ilona AU - Cohen-Katsenelson, Ksenya AU - Whitmarsh, Alan J. AU - Aronheim, Ami PY - 2015/10/23 Y2 - 2024/03/28 TI - The association of the JNK scaffold protein, WDR62, with the mixed lineage kinase 3, MLK3 JF - MAP Kinase JA - MAP Kinase VL - 4 IS - 1 SE - Original Articles DO - 10.4081/mk.2015.5307 UR - https://www.pagepressjournals.org/mk/article/view/5307 SP - AB - Mitogen-activated protein kinases (MAPKs) form a kinase tier module in which MAPK, MAP2K and MAP3K are held by scaffold proteins. The scaffold proteins serve as a protein platform for selective and spatial kinase activation. The precise mechanism by which the scaffold proteins function has not yet been fully explained. WD40-repeat protein 62, WDR62 is a novel scaffold protein of the c-Jun N-terminal kinase (JNK) pathway. WDR62 is a 1523 a.a. long protein with no significant sequence homology to a known gene. Previously WDR62 was shown to associate with JNK and MKK4/7 in a modular fashion. Here, we show that WDR62 is able to associate with multiple members of the MAP3K of the mixed lineage kinase family and we map WDR62-MLK3 interacting domains. We identify two separable interacting domains within WDR62 and MLK3 proteins that can cross associate. MLK3 association with WDR62 is independent of JNK and MKK4/7 domains and activities. CDC42 activation disrupts WDR62-MLK3 association independent of MLK3 kinase activity. ER -