Loss of hepatocellular carcinoma-related protein 1 (HCRP1) (alias VPS37A) plays a role in endocytosis receptor tyrosine kinases as member the ESCRT complex and has been linked to poor patient outcome various types epithelial cancer. To this date, molecular biological mechanisms explaining how its absence would contribute tumor progression remain unknown. Using genomic editing with CRISPR-Cas9, ...

This issue of Circulation Research includes 3 interesting studies that represent new concepts of AT1 receptor–mediated cell signaling in the cardiovascular system, which is currently of intense interest. The AT1 receptor mediates many important cardiovascular responses, including vasoconstriction, vascular and cardiac remodeling (cell proliferation, hypertrophy, and production of extracellular ...

Driver tyrosine kinase mutations are rare in sarcomas, and patterns of tyrosine phosphorylation are poorly understood. To better understand the signaling pathways active in sarcoma, we examined global tyrosine phosphorylation in sarcoma cell lines and human tumor samples. Anti-phosphotyrosine antibodies were used to purify tyrosine phosphorylated peptides, which were then identified by liquid c...

FGFR–TACC, found in different tumor types, is characterized by the fusion of a member fibroblast grown factor receptor (FGFR) tyrosine kinase (TK) family to transforming acidic coiled-coil (TACC) proteins. Because chromosome numerical alterations, hallmarks FGFR–TACC fusions are present many hematological disorders and there no data on prevalence, we studied series patients with acute myeloid l...

To investigate the range of autoinhibitory mechanisms used by TKDs (tyrosine kinase domains) from the insulin receptor family of RTKs (receptor tyrosine kinases), we determined crystal structures of TKDs from TrkA (tropomyosin receptor kinase A, a nerve growth factor receptor) and Ror2 (receptor tyrosine kinase-like orphan receptor 2, an unconventional Wnt receptor). TrkA autoinhibition closely...

The tyrosine kinase inhibitors ST271, ST638 and erbstatin inhibited phospholipase D (PLD) activity in human neutrophils stimulated by fMet-Leu-Phe, platelet-activating factor and leukotriene B4. These compounds did not inhibit phorbol ester-stimulated PLD, indicating that they do not inhibit PLD per se, but probably act at a site between the receptor and the phospholipase. In contrast, the prot...

Driver tyrosine kinase mutations are rare in sarcomas, and patterns of tyrosine phosphorylation are poorly understood. To better understand the signaling pathways active in sarcoma, we examined global tyrosine phosphorylation in sarcoma cell lines and human tumor samples. Anti-phosphotyrosine antibodies were used to purify tyrosine phosphorylated peptides, which were then identified by liquid c...

Tyrosine kinases are mainly classified into two groups, as receptor tyrosine kinase (RTK) and non-receptor tyrosine kinase (NRTK). The RTK family of transmembrane ligand-binding proteins are important mediators of the signaling cascade and includes EGFR, PDGFR (platelet-derived growth factor receptors), FGFR (fibroblast growth factor receptor) and the IR (insulin receptor). RTKs comprise 59 mem...