Functional Maturation of PAKs from Unicellular to Multicellular Organisms

摘要: A huge family of RAC/CDC42(p21)-activated Ser/Thr kinases (PAKs) are ubiquitously present in all eukaryotes from yeast to human, and play a pivotal role regulating variety normal cell functions such as actomyosin dynamics, division, migration, cardiovascular neuronal functions, when deregulated (hyperactivated) they cause diseases cancers, neurodegenerative diseases, epilepsy, learning deficits (LDs), depression, schizophrenia, inflammation, type 2 diabetes. However, the detailed mechanism that regulates PAKs vastly differs depending on each isoform or organism which it is expressed. For instance, mammalian group 1 (PAK1–3) contain an autoinhibitory domain (AID) unique Pro-rich essential for binding SH3 adaptor protein called PIX activates PAK1–3. (PAK4–6) do not bind RAC lack PIX-binding motif, PAK6 may also AID. During evolution unicellular organisms soil amoebas multicellular social marine sponges, appear evolve by series mutations exon fusions occur mainly their N-terminal regulatory domains. Here we push critical boundary during PAK evolution.