Vemurafenib Inhibits Active PTK6 in -null Prostate Tumor Cells.

Protein tyrosine kinase 6 (PTK6, also called BRK) is overexpressed and activated in human prostate cancer. Loss of the tumor suppressor PTEN, a frequent event in prostate cancer, leads to PTK6 activation at the plasma membrane and its oncogenic signaling. The small molecule inhibitor vemurafenib, also known as PLX4032, and its tool analog PLX4720 were designed to inhibit constitutively active BRAF V600E, yet they also have potent effects against PTK6.

PTEN is a protein phosphatase that targets active PTK6 and inhibits PTK6 oncogenic signaling in prostate cancer.

PTEN activity is often lost in prostate cancer. We show that the tyrosine kinase PTK6 (BRK) is a PTEN substrate. Phosphorylation of PTK6 tyrosine 342 (PY342) promotes activation, while phosphorylation of tyrosine 447 (PY447) regulates auto-inhibition.

The mcsB gene of the clpC operon is required for stress tolerance and virulence in Staphylococcus aureus.

The clpC operon in Staphylococcus aureus comprises four genes, denoted ctsR, mcsA, mcsB and clpC. A mutation within the mcsB gene resulted in hypersensitivity to heavy metal stress, temperature stress, osmotic pressure stress and oxidative stress. This mutation also resulted in sensitivity to variations in pH and lowered expression of the clpC operon under adverse extracellular conditions, as determined by quantitative real-time PCR (qRT-PCR).

Comprehensive analysis of microRNA genomic loci identifies pervasive repetitive-element origins.

MicroRNAs (miRs) are small non-coding RNAs that generally function as negative regulators of target messenger RNAs (mRNAs) at the posttranscriptional level. MiRs bind to the 3'UTR of target mRNAs through complementary base pairing, resulting in target mRNA cleavage or translation repression. To date, over 15,000 distinct miRs have been identified in organisms ranging from viruses to man and interest in miR research continues to intensify.