Nilotinib is a highly effective tyrosine kinase inhibitor used to treat Chronic Myeloid Leukemia (CML). While nilotinib successfully treats CML, a common and serious side effect is development of nilotinib-induced arterial disease (NAD) even in patients without pre-existing risk factors. This side effect is not seen with imatinib, a CML...
G protein-coupled receptors (GPCRs) are the largest family of membrane receptors in humans and play a role in nearly all physiological processes. Among GPCRs, metabotropic glutamate receptors (mGluRs) are a structurally distinct family of synaptic receptors that are essential in regulating neurotransmission and synaptic plasticity. Due to their important regulatory...
The airway epithelial cells (AECs) lining the conducting passageways of the lung secrete a variety of immunomodulatory factors. One interesting pair of molecules produces by AECs is IL-6 and prostaglandin E2 (PGE2). PGE2 limits lung inflammation and promotes bronchodilation. By contrast, IL-6 drives intense airway inflammation, remodeling, and fibrosis. The...
Chemokines, such as Stromal Derived Factor 1 (SDF-1 or CXCL12) and their G protein coupled receptors (GPCRs) are well known regulators of the development and functions of numerous tissues. CXCL12 has two receptors: CXCR4 and CXCR7 or atypical chemokine receptor 3 (ACKR3). CXCR7 has been described as an atypical “biased”...
The protein homeostasis (proteostasis) network, a critical cytoprotective system that restores homeostasis in response to molecular stress, comprises distinct pathways, including the heat-shock response, unfolded protein response, oxidative stress response, and autophagy. These distinct pathways are all co-opted by tumor cells to cope with cancer-associated stress, and their activation in...
Store-operated Ca2+ entry through Orai1 channels mediate transcriptional, proliferative, and effector cell programs in many cells and are activated through a unique inside-out mechanism involving binding of the endoplasmic reticulum Ca2+ sensor, STIM1, to cytoplasmic sites on Orai1. Mutations in Orai1 that block channel activation or evoke constitutive channel activity...
In mature neurons, postsynaptic NMDARs are segregated into two populations, synaptic and extrasynaptic NMDARs, which differ in localization, function, and associated intracellular cascades. These two pools are connected via lateral diffusion, and receptor exchange between them modulates synaptic NMDAR content (NMDAR-plasticity). Here, we identify the phosphorylation of the PDZ-ligand of...