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The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam.
- B. Lynch, N. Lambeng, B. Fuks
- Biology, ChemistryProceedings of the National Academy of Sciences…
- 29 June 2004
The experimental results suggest that SV2A is the binding site of LEV in the brain and that LEV acts by modulating the function of SV2 a, supporting previous indications that LEv possesses a mechanism of action distinct from that of other antiepileptic drugs.
The hematopoietic growth factor KL is encoded by the SI locus and is the ligand of the c-kit receptor, the gene product of the W locus
Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2.
It is shown that the soluble form of KL is generated by efficient proteolytic cleavage from a transmembrane precursor, KL-1, and that Sld, a viable steel allele, is shown to encode a biologically active secreted mutant KL protein, indicating an important function for both the soluble and the cell associate form of Kl.
Gonadal expression of c-kit encoded at the W locus of the mouse.
It was concluded that the period of expression of c-kit extends from at least as early as type A2 spermatogonia through type B sperMatogonia and into preleptotene sperMATocytes.
Molecular bases of dominant negative and loss of function mutations at the murine c‐kit/white spotting locus: W37, Wv, W41 and W.
It is shown that W37, Wv and W41 are the result of missense mutations in the kinase domain of the c‐kit coding sequence, which affect the c-kit associated tyrosine kinase to varying degrees.
Candidate ligand for the c‐kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors.
A mast cell proliferation assay is used to purify a 30 kd protein, designated KL, from conditioned medium of Balb/3T3 fibroblasts to apparent homogeneity and KL stimulates the proliferation of normal bone marrow derived mast cells but not mast cells from W mice, although both normal and mutant mast cells respond similarly to IL‐3.
Alternative splicing of interleukin-33 and type 2 inflammation in asthma
- E. Gordon, L. Simpson, J. Fahy
- Biology, MedicineProceedings of the National Academy of Sciences
- 18 July 2016
It is concluded that IL- 33 isoforms activate basophils and mast cells to drive type 2 inflammation in chronic stable asthma, and novel IL-33 inhibitors will need to block all biologically active isoforms.
Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice--evidence for an impaired c-kit kinase in mutant mice.
It is demonstrated that the c-kit associated tyrosine-specific protein kinase is functionally impaired in W/WV mast cells, thus providing a molecular basis for understanding the developmental defects that result from mutations at the W locus.
The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase.
Nucleotide sequence analysis of mutant complementary DNAs revealed a missense mutation that replaces aspartic acid with asparagine at position 790 in the c-kit protein product, a conserved residue in all protein kinases.
Identification of a Chemical Probe for Bromo and Extra C-Terminal Bromodomain Inhibition through Optimization of a Fragment-Derived Hit
- P. Fish, P. Filippakopoulos, John D. Trzupek
- Biology, ChemistryJournal of medicinal chemistry
- 25 October 2012
The discovery and structure–activity relationship (SAR) of a novel, small-molecule chemical probe for BET family inhibition that was identified through the application of structure-based fragment assessment and optimization techniques has yielded a potent, selective compound with cell-based activity (PFI-1) that may further add to the understanding of BET family function within the bromodomains.