Kinases associate with scaffold proteins that regulate signaling by providing critical spatial and temporal specificities. Extracellular regulated kinases (ERK) are mainly activated by mitogenic stimuli such as growth factors and hormones, whereas c-Jun N-terminal kinases (JNK) and p38 kinases respond predominantly to stress stimuli. MAPKs can be grouped into three classes depending on the stimuli they respond to. MAPK proteins are serine-threonine kinases that can phoshorylate targets in the cytoplasm or the nucleus in response to stimuli such as mitogenic or stress signals. The mitogen-activated protein kinase (MAPK) pathways are evolutionary conserved signaling pathways used by eukaryotic cells to regulate gene expression during diverse processes such as proliferation, differentiation, apoptosis, adaptation to changes in their environment, and so on (for a review, see ). Our data therefore suggest that the Enhancer of Trithorax and Polycomb Corto could participate in regulating vein and intervein genes during wing tissue development in response to ERK signaling. Interestingly, its phosphorylation pattern differs between cytoplasm and nucleus and changes upon ERK activation. Furthermore, Corto, ERK and dMP1 co-localize on several sites on polytene chromosomes, suggesting that they regulate gene expression directly on chromatin. Although Corto, ERK and dMP1 are present in both cytoplasmic and nucleus compartments, they interact exclusively in nucleus extracts. Genetic interactions show that corto and dMP1 act together to antagonize rolled (which encodes ERK) in the future intervein cells, thus promoting intervein fate. Functional relationships during wing development between a chromatin regulator, the Enhancer of Trithorax and Polycomb Corto, ERK and its scaffold protein dMP1, are examined here. In Drosophila, dMP1, that encodes an ERK scaffold protein, regulates ERK signaling during wing development and contributes to intervein and vein cell differentiation. These kinase modules are associated with scaffold proteins that control their activity. This dependence on supramolecular assembly introduces new possibilities for regulation and control.Mitogen-activated protein kinase (MAPK) cascades (p38, JNK, ERK pathways) are involved in cell fate acquisition during development. This establishes proof of concept for exploiting peptides stabilised in de novo coiled coils as inhibitors of PPIs. Furthermore, the heterodimeric system affords control as inhibition occurs only when both the grafted peptide and its designed partner are present. The resulting synthetic peptides selectively inhibit a cognate MCL-1/BID complex in the mid-nM range. Next, these residues are grafted onto the exposed surfaces of de novo designed homodimeric or heterodimeric coiled-coil peptides. First, computational alanine scanning is used to identify key α-helical residues from NOXA-B that contribute to the interface. Here we present a strategy to target α-helix-mediated PPIs that exploits de novo coiled-coil assemblies and test this using the MCL-1/NOXA-B PPI. PPIs with α-helical components are appealing targets given that the secondary structure is well understood and can be mimicked or stabilised to render small-molecule and constrained-peptide-based inhibitors. Therefore, improved approaches to target and disrupt PPIs would provide tools for chemical biology and leads for therapeutic development. Protein–protein interactions (PPIs) play pivotal roles in the majority of biological processes.

Protein scaffold interaction