Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human stem cell factor (SCF), also termed c-Kit ligand (KL), is a hematopoietic growth factor produced by mesenchymal cells that induces proliferation of bone marrow progenitor cells, megakaryocytes, and mast cells via interaction with c-Kit, its cognate receptor. Expression of the c-kit gene was identified in human platelets by the polymerase chain reaction technique. The presence of the c-Kit receptor was demonstrated by the specific binding of 125I-KL/SCF to ADP-stimulated platelets. The identity of the c-Kit protein was confirmed by immunoreactivity with an anti-c-Kit-specific antibody and by its characterization as a phosphotyrosine-containing protein. Under constitutive conditions, c-Kit was found to be tyrosine-phosphorylated and was associated with a 85-kDa phosphoprotein that could be a fragment of phosphatidylinositol 3-kinase. These data indicate the presence of a new platelet surface molecule that could function in platelet activation. We demonstrate that the secondary wave of platelet aggregation and serotonin secretion induced by epinephrine and ADP, but not by the thromboxane analog U46619, was augmented by KL/SCF. The effect of KL/SCF on epinephrine/ADP-induced platelet activation appeared to be mediated in part through the thromboxane pathway. These data suggest that KL/SCF could modulate hemostasis via interaction with platelets, particularly in conditions where mesenchymal cells are exposed to circulating blood elements, such as in wound healing or atherosclerosis.
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PMID:Human kit ligand (stem cell factor) modulates platelet activation in vitro. 752 Apr 41

Receptor tyrosine kinase (RTK) enzymes regulate cell signaling pathways and so are an important target for cancer chemotherapy. Current inhibitors of c-kit, a key RTK stem cell factor receptor, are inactive against the most common mutated variant Asp816Val, associated with highly malignant cancers. Recent combined experimental/simulation work has highlighted the utility of the ellipticine pharmacore in inhibiting mutant c-kit, and the present simulation study applies a combination of high-level simulation tools to probe further the binding of ellipticine-based derivatives to c-kit. We find a large preference for protonation of bound ellipticine, which stabilizes the negative protein residues that coordinated ADP.Mg (2+) in the native complex. The resulting ellipticine inhibitor binding mode resembles the native nucleotide complex and serves to explain some existing experimental data on binding specificities, indicating that functionalization at the C4/C5 sites of ellipticine derivatives may be important for the design of novel nucleotide analogues that inhibit mutant c-kit.
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PMID:Computer simulations reveal a novel nucleotide-type binding orientation for ellipticine-based anticancer c-kit kinase inhibitors. 1875 82