Design of allele-specific inhibitors to probe protein kinase signaling

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Design of allele-specific inhibitors to probe protein kinase signaling

BACKGROUND Deconvoluting protein kinase signaling pathways using conventional genetic and biochemical approaches has been difficult because of the overwhelming number of closely related kinases. If cell-permeable inhibitors of individual kinases could be designed, the role of each kinase could be systematically assessed. RESULTS We have devised an approach combining chemistry and genetics to ...

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Design of allele-specific protein methyltransferase inhibitors.

Protein arginine methyltransferases, which catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to arginine side chains in target proteins, regulate transcription, RNA processing, and receptor-mediated signaling. To specifically address the functional role of the individual members of this family, we took a "bump-and-hole" approach and designed a series of N(6)-substituted S-a...

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Inhibitors of Protein Kinase Signaling Pathways

Protein kinases are enzymes that covalently modify proteins by attaching phosphate groups (from ATP) to serine, threonine, and/or tyrosine residues. In so doing, the functional properties of the protein kinase’s substrates are modified. Protein kinases transduce signals from the cell membrane into the interior of the cell. Such signals include not only those arising from ligand–receptor interac...

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Modulation of protein kinase signaling by protein phosphatases and inhibitors.

Protein tyrosine phosphatases (PTPs) form a large family of enzymes that serve as key regulatory components in signal transduction pathways. Defective or inappropriate regulation of PTP activity leads to aberrant tyrosine phosphorylation, which contributes to the development of many human diseases. In addition to controlling the phosphorylation states of protein kinase substrates, PTPs can also...

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ژورنال

عنوان ژورنال: Current Biology

سال: 1998

ISSN: 0960-9822

DOI: 10.1016/s0960-9822(98)70198-8