Protein kinases phosphorylate long disordered regions in intrinsically disordered proteins. (28th November 2019)

• Record Type: Journal Article
• Authors: Koike, Ryotaro; Amano, Mutsuki; Kaibuchi, Kozo; Ota, Motonori
• Is Part Of: Protein science. Volume 29:Number 2(2020)
• Page Start: 564
• Page End: 571
• Publication Date: 2019-11-28
• Subjects: database -- phosphoprotein -- phosphorylation -- phosphosites -- signal transduction; Proteins -- Periodicals; 572.6
• DOI: 10.1002/pro.3789
• Languages: English
• ISSNs: 0961-8368

Abstract

Abstract: Phosphorylation is a major post‐translational modification that plays a central role in signaling pathways. Protein kinases phosphorylate substrates (phosphoproteins) by adding phosphate at Ser/Thr or Tyr residues (phosphosites). A large amount of data identifying and describing phosphosites in phosphoproteins has been reported but the specificity of phosphorylation is not fully resolved. In this report, data of kinase‐substrate pairs identified by the Kinase‐Interacting Substrate Screening (KISS) method were used to analyze phosphosites in intrinsically disordered regions (IDRs) of intrinsically disordered proteins. We compared phosphorylated and nonphosphorylated IDRs and found that the phosphorylated IDRs were significantly longer than nonphosphorylated IDRs. The phosphorylated IDR is often the longest IDR (71%) in a phosphoprotein when only a single phosphosite exists in the IDR, and when the phosphoprotein has multiple phosphosites in an IDR(s), the phosphosites are primarily localized in a single IDR (78%) and this IDR is usually the longest one (81%). We constructed a stochastic model of phosphorylation to estimate the effect of IDR length. The model that accounted for IDR length produced more realistic results when compared with a model that excluded the IDR length. We propose that the IDR length is a significant determinant for locating kinase phosphorylation sites in phosphoproteins.