Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer.

Even though SYK and ZAP70 kinases share high sequence homology and serve analogous functions, their expression in B and T cells is strictly segregated throughout evolution. Here, we identified aberrant ZAP70 expression as a common feature in a broad range of B cell malignancies. We validated SYK as the kinase that sets the thresholds for negative selection of autoreactive and premalignant clones.

Islets from human donors with higher but not lower hemoglobin A1c levels respond to gastrin treatment in vitro.

Gastrin is a peptide hormone, which in combination with other factors such as TGFα, EGF or GLP-1, is capable of increasing beta cell mass and lowering blood glucose levels in adult diabetic mice. In humans, administration of a bolus of gastrin alone induces insulin secretion suggesting that gastrin may target islet cells. However, whether gastrin alone is sufficient to exert an effect on isolated human islets has been controversial and the mechanism remained poorly understood.

Darpp-32 and t-Darpp protein products of PPP1R1B: Old dogs with new tricks.

The PPP1R1B gene is located on chromosome 17q12 (39,626,208-39,636,626[GRCh38/hg38]), which codes for multiple transcripts and two experimentally-documented proteins Darpp-32 and t-Darpp. Darpp-32 (Dopamine and cAMP Regulated Phosphoprotein), discovered in the early 1980s, is a protein whose phosphorylation is upregulated in response to cAMP in dopamine-responsive tissues in the brain. It's phosphorylation profile modulates its ability to bind and inhibit Protein Phosphatase 1 activity, which, in turn, controls the activity of hundreds of phosphorylated proteins.

t-Darpp Activates IGF-1R Signaling to Regulate Glucose Metabolism in Trastuzumab-Resistant Breast Cancer Cells.

Increased glycolysis and glucose dependence is a hallmark of malignancy that enables tumors to maximize cell proliferation. In HER2 cancers, an increase in glycolytic capacity is associated with trastuzumab resistance. IGF-1R activation and t-Darpp overexpression both confer trastuzumab resistance in breast cancer.

Novel interaction between the major bacterial heat shock chaperone (GroESL) and an RNA chaperone (CspC).

The heat shock response is one of the main global regulatory networks in all organisms and involves an increased cellular level of chaperones and proteases to enable correct protein folding and balanced growth. One of the major heat shock chaperones in Escherichia coli is GroESL, composed of GroES and GroEL (the bacterial Hsp10 and Hsp60 homologues), which is essential for refolding of misfolded proteins. GroESL was previously shown to play a role in the regulation of the heat shock response by promoting the proteolysis of the regulatory protein--sigma32 (RpoH), the heat shock transcription activator.

Sequence features of E. coli mRNAs affect their degradation.

Degradation of mRNA in bacteria is a regulatory mechanism, providing an efficient way to fine-tune protein abundance in response to environmental changes. While the mechanisms responsible for initiation and subsequent propagation of mRNA degradation are well studied, the mRNA features that affect its stability are yet to be elucidated. We calculated three properties for each mRNA in the E.