Biological crosstalk refers to instances in which one or more components of one signal transduction pathway affects another. In the past few years, evidence for extensive crosstalk between PTMs has accumulated, with the competitive interplay between O-GlcNac and O-phosphorylation being one of the first and best-established examples. The advent of highly sensitive MS-based strategies for large-scale PTM analysis substantially improved our knowledge about PTM and the co-occurrence/crosstalk of PTMs. As one of the leading omics industry company in the world, we are open to help you with TM Crosstalk Analysis Service.
Protein function is largely destined by three-dimensional and surface structure, and respective structural subunits can be divided into longer (>30 amino acids) modular domains and shorter (more than ten amino acids) linear motifs. Both participate in generating, transmitting, and processing cellular signals. Linear motifs present modifiable sequence stretches that can be “read” and processed by modular domains. Depending on whether these modular domains recognize, transfer, or remove a PTM, they are termed “readers,”“writers,” or “erasers”, as illustrated in the follow graph. In case of phosphorylation, kinases act as writers, whereas domains which recognize the respective residues (e.g. SH2 domains in case of pTyr) are considered as readers and phosphatases as erasers. Which proteins, in particular, act as readers, writers, and erasers depends on the existing PTM pattern of the target protein.
Generally, PTM crosstalk can be principally classified into positive and negative forms. In positive crosstalk, the initial PTM serves as an active trigger for the addition or removal of a second PTM, or as a recognition site for other proteins, as, for instance, in phosphorylation-dependent ubiquitination and SUMOylation. In contrast, negative crosstalk can include direct competition of two PTMs for the same amino acid or indirect effects when a specific PTM masks the recognition site for second PTM, thus preventing its addition and/or removal.
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