Figure 8
From: RACK1 is involved in endothelial barrier regulation via its two novel interacting partners
Proposed model for prenylation and redistribution of TIMAP upon cAMP/PKA activation. (A) In EC monolayer non-phosphorylated TIMAP is localized in the nucleus, also in the cytosol bound to RACK1, while prenylated and phosphorylated form of TIMAP is at the cell membrane. (B C) Upon PKA/GSK3β activation TIMAP in the RACK1 complex is phosphorylated resulting in conformation change, the C-terminal CAAX box becomes accessible for prenylation by farnesyl transferase (FT) bound also to RACK1. The prenylated TIMAP relocalizes to the cell membrane and RACK1 gets refilled with TIMAP from the nuclear pool. When that pool is exhausted, the amount of RACK1-TIMAP complex becomes low. Based on our previous result [5] PP1c is shown in complex with both non- and phosphorylated TIMAP, colors indicate different phosphatase activities of the complex. Representation of MYPT3 in [47] was used in the proposed conformational changes of TIMAP.