A Keith Dunker
Indiana University , USA
Title: Intrinsically disordered proteins link alternative splicing and post-translational modifications to complex cell signaling and regulation
Biography
Biography: A Keith Dunker
Abstract
Intrinsically disordered proteins and regions (IDPs and IDRs) lack well-defined tertiary structures, yet carry out various important cellular functions, especially those associated with cell signaling and regulation. In eukaryotes, IDPs and IDRs contain the preferred loci for both alternative splicing (AS) and many post-translational modifi cations (PTMs). Furthermore, AS and/or PTMs at these loci generally alter the signaling outcomes associated with these IDPs or IDRs. However, the prevalence of such functional modulations remains unknown. Also, the signal-altering mechanisms by which AS, and PTMs modulate function and the extent to which AS and PTMs collaborate in their signaling modulations have not been well defined for particular protein examples. Here, we focus on three important signaling and regulatory IDR-containing protein families in humans, namely G-protein coupled receptors (GPCRs), which are transmembrane proteins, the nuclear factors of activated T-cells (NFATs), which are transcription factors (TFs), and the Src family kinases (SFKs), which are signaling enzymes. The goal here is to determine how AS and PTMs individually alter the outcomes of the signaling carried out by the various IDRs and to determine whether AS and PTMs work together to bring about diff erential cellular responses. We also present data indicating that a wide range of other signaling IDPs or IDRs undergo both AS- and PTM-based modifi cations, suggesting that they, too, likely take advantage of signal outcome modulations that result from collaboration between these two events. Hence, we propose that the widespread cooperation of IDPs, AS and/or PTMs substantially contributes to the vast complexity of eukaryotic cell signaling systems.