RT Journal Article ID 38b0a55b1c57f6fb A1 Vandamme, Drieke A1 Herrero, Ana A1 Al-Mulla, Fahd A1 Kolch, Walter T1 Regulation of the MAPK Pathway by Raf Kinase Inhibitory Protein JF Critical Reviews™ in Oncogenesis JO CRO YR 2014 FD 2014-11-24 VO 19 IS 6 SP 405 OP 415 K1 lipid binding K1 MAPK signaling K1 pathology K1 Raf K1 RKIP AB The Raf kinase inhibitor protein 1 (RKIP-1) was the first reported endogenous inhibitor of Raf-1-MEK-ERK/MAPK cascade, by interfering with the phosphorylation of MEK by Raf-1. However, RKIP's functions related to the MAPK signaling are far more complex. Newer data indicate that by modulating different protein-protein interactions, RKIP is involved in fine-tuning cell signaling, modulating ERK dynamics, and regulating cross talk between different pathways. Here, we describe the molecular mechanisms by which RKIP controls MAPK signaling at different levels and vice versa and its regulation via feedback phosphorylation. We also focus on several discrepancies and questions that remain, such as the RKIP binding regulation by Raf-1 N-region phosphorylation, the possible B-Raf inhibition, and the effects of RKIP-lipid binding. We also describe how RKIP's role as key signaling modulator of many cell fate decisions leads to the fact that fine control of RKIP activity and regulation is crucial to avoid pathological processes, such as metastasis, pulmonary arterial hypertension, and heart failure. PB Begell House LK https://www.dl.begellhouse.com/journals/439f422d0783386a,492698d1102624fd,38b0a55b1c57f6fb.html