Upon engagement of the TCR by antigen presented on major histocompatibility complex (MHC) molecules, the Src family kinase Lck is activated and proceeds to phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the ε, δ, γ and ζ subunits of the TCR. Phosphorylated ITAMs promote the recruitment and subsequent activation of another tyrosine kinase ZAP-70. Two known substrates of...

Abstract Introduction β-catenin is a protein molecule of the E-cadherin/catenin adhesion complex that maintains epithelial cell-cell and intracellular signalling. The mutation overexpression leads to cancer, including pancreatic ductal adenocarcinoma (PDAC). FLYWCH1 newly identified with zinc-finger type DNA-binding domain interacts nuclear β-catenin, leading increased cell-matrix in cancer ste...

Diverse extracellular signals are coupled at the plasma membrane to intracellular signal transduction pathways and the cytoskeleton. Members of a ubiquitous multidomain family of proteins, the MAGUK proteins, are emerging as common mediators of this coupling.

Emerging evidence indicates that complex spatial gradients and (micro)domains of signalling activities arise from distinct cellular localization of opposing enzymes, such as a kinase and phosphatase, in signal transduction cascades. Often, an interacting, active form of a target protein has a lower diffusivity than an inactive form, and this leads to spatial gradients of the protein abundance i...

SUMOylation is a highly transient post-translational protein modification. Attachment of SUMO to target proteins occurs via a number of specific activating and ligating enzymes that form the SUMO-substrate complex, and other SUMO-specific proteases that cleave the covalent bond, thus leaving both SUMO and target protein free for the next round of modification. SUMO modification has major effect...

Abstract How Merlin-intact meningiomas arise in the absence of NF2/Merlin inactivation is incompletely understood. Here, we integrate single-cell RNA sequencing 86,000 cells from meningioma xenografts with APEX2 proteomic proximity-labelling mass spectrometry and functional biochemical approaches to discover Merlin Serine 13 (S13) dephosphorylation drives Wnt signalling cell proliferation. Cell...

Abstract Estrogen deficiency during post-menopausal osteoporosis leads to osteoclastogenesis and bone loss. Increased pro-osteoclastogenic signalling (RANKL/OPG) by osteocytes occurs following estrogen withdrawal (EW) is associated with impaired focal adhesions (FAs) a disrupted actin cytoskeleton. RANKL production mediated Hedgehog in osteocytes, pathway the primary cilium, ciliary structure t...

There is an intimate, yet poorly understood, link between cellular metabolic status, cell signalling and transcription. Central metabolic pathways are under the control of signalling pathways and, vice versa, the cellular metabolic profile influences cell signalling through the incorporation of various metabolic sensors into the signalling networks. Thus information about nutrients availability...