A specific protein kinase that phosphorylates Ser60, Ser59, or Ser58 of 14-3-3beta, eta, or zeta, respectively, only in the presence of sphingosine (Sph) or N,N-dimethyl-Sph (DMS), was termed "sphingosine-dependent protein kinase-1" (SDK1) [J. Biol. Chem. 273(34) (1998) 21834]. We have now identified SDK1 as a protein having the same amino acid sequence as in the C-terminal-half kinase domain of PKCdelta, with approximately 40 kDa molecular mass, based on large-scale purification of a protein from rat liver, and partial sequence using three different combinations of LC-MS or LC-MS/MS with respective search engine. PKCdelta did not display any SDK1 activity and PKCdelta activity was inhibited by Sph and DMS. However, strong SDK1 activity, only in the presence of Sph or DMS, became detectable when PKCdelta was incubated with caspase-3, which releases the approximately 40 kDa kinase domain.
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http://dx.doi.org/10.1016/s0006-291x(03)01070-2 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFJ Pediatr Hematol Oncol
January 2025
Department of Pediatrics, West China Second University Hospital, Sichuan University, Sichuan, China.
Langerhans cell histiocytosis (LCH) is characterized genetically by diverse gene mutations of the mitogen-activated protein kinase signaling cascade. BRAFN486_T491delinsK mutation is a rare mutation that involves the β2-αC ring domain, causing activation of the mitogen-activated protein kinase pathway, and is predicted to be resistant to the chemotherapy and BRAFV600E inhibitor in adult LCH cases. Here, we report a childhood LCH case with this novel BRAF mutation and had a good response to conventional chemotherapy.
View Article and Find Full Text PDFPlant Cell
January 2025
State Key Laboratory of Plant Environmental Resilience, China Agricultural University, Beijing 100193, China.
Salt stress causes ion toxicity in plant cells and limits plant growth and crop productivity. Sodium ions (Na+) are transported out of the cell and sequestered in the vacuole for detoxification under salt stress. The salt excretion system is controlled by the SALT OVERLY SENSITIVE (SOS) pathway, which consists of the calcium sensors SOS3 and SOS3-LIKE CALCIUM BINDING PROTEIN 8, the protein kinase SOS2, and the plasma membrane Na+/H+ antiporter SOS1.
View Article and Find Full Text PDFBiochem J
January 2025
University of Pittsburgh School of Medicine, Pittsburgh, United States.
The sodium phosphate cotransporter-2A (NPT2A) mediates basal and parathyroid hormone (PTH)- and fibroblast growth factor-23 (FGF23)-regulated phosphate transport in proximal tubule cells of the kidney. Both basal and hormone-sensitive transport require sodium hydrogen exchanger regulatory factor-1 (NHERF1), a scaffold protein with tandem PDZ domains, PDZ1 and PDZ2. NPT2A binds to PDZ1.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Cancer Innovation Laboratory, National Cancer Institute, Frederick, Maryland 21702, United States.
mTOR plays a crucial role in PI3K/AKT/mTOR signaling. We hypothesized that mTOR activation mechanisms driving oncogenesis can advise effective therapeutic designs. To test this, we combined cancer genomic analysis with extensive molecular dynamics simulations of mTOR oncogenic variants.
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