The RNA binding protein YBX1 is a key regulator of epidermal progenitor cell senescence that prevents the mRNA translation critical senescence-associated secretory phenotypes (SASP) transcripts such as CXCL1 and IL8. Decreased levels during aging enables production SASP-related proteins subsequent induction senescence. Posttranslational modifications YBX1, phosphorylation at Ser 102, can modify...

Cancer treatment often tends to involve direct targeting enzymes essential for the growth and proliferation of cancer cells. The aim of this study was the recognition of the possible role of selected protein kinases: PI3K, ERK1/2, and mTOR in cell proliferation and cell cycle in malignant melanoma. We investigated the role of protein kinase inhibitors: U0126 (ERK1/2), LY294002 (PI3K), rapamycin...

The role of G protein-coupled receptors and their ligands in intestinal epithelial cell signaling and proliferation is poorly understood. Here, we demonstrate that arginine vasopressin (AVP) induces multiple intracellular signal transduction pathways in rat intestinal epithelial IEC-18 cells via a V(1A) receptor. Addition of AVP to these cells induces a rapid and transient increase in cytosolic...

Allosteric inhibitors of Abl kinase are being explored in the clinic, often combination with ATP-site kinase. However, there conflicting data on whether both ATP-competitive and myristoyl-site allosteric can simultaneously bind Here, we determine is synergy or antagonism between Abl. We observe that clinical not synergistic ABL inhibitors, however, conformation-selective modulate global conform...

NF-?B-inducing kinase (NIK) is a key enzyme in the noncanonical NF-?B pathway, of interest treatment variety diseases including cancer. Validation NIK as drug target requires potent and selective inhibitors. The protein contains cysteine residue at position 444 back pocket active site, unique within kinome. Analysis existing inhibitor scaffolds early structure-activity relationships (SARs) led ...

Surfactant protein A (SP-A), the most abundant pulmonary surfactant protein, plays a role in innate host defense and blocks the inhibitory effects of serum proteins on surfactant surface tension-lowering properties. SP-A mRNA and protein are downregulated by phorbol esters (TPA) via inhibition of gene transcription. We evaluated the TPA signaling pathways involved in SP-A inhibition in a lung c...

BACKGROUND Autophagy is a highly conserved and regulated cellular process employed by living cells to degrade proteins and organelles as a response to metabolic stress. We have previously reported that eukaryotic elongation factor-2 kinase (eEF-2 kinase, also known as Ca(2+)/calmodulin-dependent protein kinase III) can positively modulate autophagy and negatively regulate protein synthesis. The...

Protein kinase signaling cascades control most aspects of cellular function. The ATP binding domains of signaling protein kinases are the targets of most available inhibitors. These domains are highly conserved from mammals to flies. Herein we describe screening of a library of small molecule inhibitors of protein kinases for their ability to increase Drosophila lifespan. We developed an assay ...

Antidepressant-sensitive serotonin (5-hydroxytryptamine, 5HT) transporters (SERTs) are responsible for efficient synaptic clearance of extracellular 5HT. Previously (Qian, Y., Galli, A., Ramamoorthy, S., Risso, S., DeFelice, L. J., and Blakely, R. D. (1997) J. Neurosci. 17, 45-47), we demonstrated that protein kinase (PKC)-linked pathways in transfected HEK-293 cells lead to the internalization...