ROCK1/2 signaling contributes to corticosteroid-refractory acute graft-versus-host disease.

Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase.

The Small GTPase RHOA Links SLP65 Activation to PTEN Function in Pre B Cells and Is Essential for the Generation and Survival of Normal and Malignant B Cells.

The generation, differentiation, survival and activation of B cells are coordinated by signals emerging from the B cell antigen receptor (BCR) or its precursor, the pre-BCR. The adaptor protein SLP65 (also known as BLNK) is an important signaling factor that controls pre-B cell differentiation by down-regulation of PI3K signaling. Here, we investigated the mechanism by which SLP65 interferes with PI3K signaling.

Circulatory miRNA-155, miRNA-21 target PTEN expression and activity as a factor in breast cancer development.

Breast cancer is a complex disease with multiple factors involved in its pathophysiological development. genetic mutations of BRCA1, BRCA2 and p53 are among the most well-studied factors. The role of other genetic factors like altered expression profiles, SNPs in the regulatory regions of different genes or epigenetic factors like promoter methylation and histone modifications are also well studied but no solid understanding is available on distinct key players triggering malignancy in breast cancer, (Phosphatase and tensin homolog) PTEN is known to be a crucial tumor suppressor as it has been reported to be missing or abnormally expressed in many cancer cells.

FoxO1 induces Ikaros splicing to promote immunoglobulin gene recombination.

Somatic rearrangement of immunoglobulin (Ig) genes is a key step during B cell development. Using pro-B cells lacking the phosphatase Pten (phosphatase and tensin homolog), which negatively regulates phosphoinositide-3-kinase (PI3K) signaling, we show that PI3K signaling inhibits Ig gene rearrangement by suppressing the expression of the transcription factor Ikaros. Further analysis revealed that the transcription factor FoxO1 is crucial for Ikaros expression and that PI3K-mediated down-regulation of FoxO1 suppresses Ikaros expression.