The assembly of complexes following the detection of extracellular signals is often controlled by signaling proteins comprising multiple peptide binding modules. The SRC homology (SH)3 family represents the archetypical modular protein interaction module, with ~300 annotated SH3 domains in humans that regulate an impressive array of signaling processes. We review recent findings regarding the allosteric contributions of SH3 domains host protein context, their phosphoregulation, and their roles in phase separation that challenge the simple model in which SH3s are considered to be portable domains binding to specific proline-rich peptide motifs.
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http://dx.doi.org/10.1016/j.tibs.2022.04.005 | DOI Listing |
Arch Microbiol
January 2025
Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia.
Bacteriophages produce endolysins at the end of the lytic cycle, which are crucial for lysing the host cells and releasing virion progeny. This lytic feature allows endolysins to act as effective antimicrobial alternatives when applied exogenously. Staphylococcal endolysins typically possess a modular structure with one or two enzymatically active N-terminal domains (EADs) and a C-terminal cell wall binding domain (CBD).
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.
View Article and Find Full Text PDFBiomolecules
January 2025
Institute of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
The Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is a multidomain protein consisting of two protein-protein interaction domains, the Src homology 2 (SH2) domain, and the proline-rich region (PRR), as well as three phosphoinositide-binding domains, the pleckstrin homology-like (PHL) domain, the 5-phosphatase (5PPase) domain, and the C2 domain. SHIP1 is commonly known for its involvement in the regulation of the PI3K/AKT signaling pathway by dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P) at the D5 position of the inositol ring. However, the functional role of each domain of SHIP1 for the regulation of its enzymatic activity is not well understood.
View Article and Find Full Text PDFChemosphere
January 2025
Department of Pharmacology/Toxicology, School of Medicine, Daegu Catholic University, Daegu, Republic of Korea. Electronic address:
Perfluorooctane sulfonate (PFOS), a widely distributed and persistent organic pollutant, is known to cause immune dysfunction. In a previous study, we reported that PFOS modestly increases mast cell activation. However, its effects on FcεRI (a high-affinity IgE receptor)-mediated mast cell activation, a pivotal process in inflammatory allergic reactions and innate immunity, have not been clearly demonstrated.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China. Electronic address:
Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) plays a dual role in cancer initiation and progression. Identifying signals that modulate the function of SHP2 can improve current therapeutic approaches for IFN-α/β in HCC. We showed that cAMP-dependent protein kinase A (PKA) suppresses IFN-α/β-induced JAK/STAT signaling by increasing the phosphatase activity of SHP2, promoting the dissociation of SHP2 from the receptor for activated C-kinase 1 (RACK1) and binding to STAT1.
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