Publications by authors named "A T Sorkin"

Article Synopsis
  • Ligand binding to EGFR activates Rho GTPases, leading to changes in the actin cytoskeleton that promote cell movement and invasion.
  • The study used live-cell imaging to show that VAV2, which helps activate Rho GTPases, is co-endocytosed with EGFR in cancer cells, highlighting its role in metastasis and poor outcomes in head-and-neck cancer.
  • Chemotactic migration of these cancer cells towards EGF relies on both VAV2 and clathrin-mediated endocytosis, with persistent signaling events occurring in endosomes, crucial for EGFR-driven cell movement.
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Monoamine transporters function in neuronal membranes to control extracellular concentrations of their substrates. Cell-surface expression of transporters is regulated by substrates and intracellular signaling, but the underlying mechanisms remain unclear. Here, we found that substrates of the dopamine transporter (DAT), amphetamine and dopamine, synergize with protein kinase C (PKC)-dependent DAT ubiquitination to markedly elevate clathrin-mediated endocytosis of DAT, which is accompanied by DAT movement out of plasma membrane protrusions with a negative curvature.

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Article Synopsis
  • The study explores how low-affinity EGFR ligands, specifically epiregulin (EREG), activate the EGFR in cells during processes like collective cell migration.
  • It reveals that during this migration, certain patterns of signal activation occur that depend on the shedding of EGFR ligands and the structural integrity of cell junctions.
  • The absence of EREG in mice leads to slower ERK wave propagation and less effective cell movement, suggesting that low-affinity ligands are crucial for quick signaling between cells.
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Epidermal growth factor receptor ligands (EGFRLs) consist of seven proteins. In stark contrast to the amassed knowledge concerning the epidermal growth factor receptors themselves, the extracellular dynamics of individual EGFRLs remain elusive. Here, employing fluorescent probes and a tool for triggering ectodomain shedding of EGFRLs, we show that EREG, a low-affinity EGFRL, exhibits the most rapid and efficient activation of EGFR in confluent epithelial cells and mouse epidermis.

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Dopamine transporter (DAT) controls dopamine signaling in the brain through the reuptake of synaptically released dopamine. DAT is a target of abused psychostimulants such as amphetamine (Amph). Acute Amph administration induces transient DAT endocytosis, which, among other Amph effects on dopaminergic neurons, elevates extracellular dopamine.

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