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SH2 domains are widespread protein-binding modules that recognize phosphotyrosines and play central roles in intracellular signalling pathways. The SH2 domain of the human protein tyrosine kinase Fyn has been expressed, purified and crystallized in the unbound state and in complex with a high-affinity phosphotyrosine peptide. X-ray data were collected to a resolution of 2.00 Å for the unbound form and 1.40 Å for the protein in complex with the phosphotyrosine peptide.
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http://dx.doi.org/10.1107/S1744309112004186 | DOI Listing |
Proteomics
August 2025
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
T-cell receptor (TCR) signaling plays a crucial role in various biological processes and is usually studied using global mass spectrometry-based phosphoproteomic studies. Despite advancements in targeted mass spectrometry-based assays for protein quantification, their application in studying signaling processes, for example, reproducible measurements of post-translational modifications (PTMs) such as phosphorylation, remains limited. Tyrosine phosphorylation is critical for many signaling pathways but presents challenges due to the low abundance of phosphotyrosine-containing peptides.
View Article and Find Full Text PDFBlood Adv
August 2025
Temple University School of Medicine, Philadelphia, Pennsylvania, United States.
Spleen tyrosine kinase (Syk) is expressed in a variety of hemopoietic cells. Its phosphorylation regulates downstream signaling events upon stimulation of receptors containing an immune tyrosine activation motif (ITAM), like glycoprotein VI (GPVI), or a hemITAM, including the C-type lectin-like receptor II-type (CLEC-2). This study focuses on the role of a specific phosphorylation site, Tyrosine 317, in the regulation of Syk function.
View Article and Find Full Text PDFActa Physiol (Oxf)
September 2025
Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Aim: Tendons are fibrous tissues connecting muscles to bones, providing joint stability and enabling movement. Adaptor proteins regulate cellular processes essential for maintaining tendon function. Phosphotyrosine-binding domain-containing engulfment adaptor protein 1 (GULP1) participates in multiple cellular activities; however, its specific role in tendons remains unclear.
View Article and Find Full Text PDFJ Neurosci
July 2025
Center for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962
Endosomal system dysfunction within neurons is a prominent early feature of Alzheimer's disease (AD) pathology. Multiple AD risk factors are regulators of endocytosis and known to cause hyperactivity of the early endosome small GTPase rab5, resulting in neuronal endosomal pathway disruption and cholinergic neurodegeneration. Adaptor protein containing Pleckstrin homology domain, Phosphotyrosine binding domain, Leucine zipper motif (APPL1), an important rab5 effector protein and signaling molecule has been shown in vitro to interface between endosomal and neuronal dysfunction through a rab5-activating interaction with the BACE1-generated C-terminal fragment of amyloid precursor protein (APP-βCTF), a pathogenic APP fragment generated within endosomal compartments.
View Article and Find Full Text PDFbioRxiv
June 2025
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, 02903.
Many commercial desalting products exist for pre-MS peptide cleanup, although few exist that can handle the high protein input (≥ 4 mg) required for phosphotyrosine enrichment. For these desalting products, the technical aptitude required for effective and organized desalting is often a barrier to entry for new users. Here, we evaluate four commercially available desalting techniques with varying degrees of automation, operational organization, and chemistries to determine the most cost-effective, user-friendly, and sensitive technique for protein profiling and phosphotyrosine (pY) enrichment.
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