Abstract:
:PLK1 (polo-like kinase 1) is a key mitotic kinase and a therapeutic target in the treatment of proliferative diseases. Here we investigate the relative substrate specificity and pharmacological relatedness of PLK1, -2, -3, and -4 that together comprise a conserved family of Ser/Thr kinases (PLK family). We report consensus substrate sequences for PLK2, -3, and -4 and an expanded consensus sequence for PLK1, which we use to design an optimal peptide substrate, PLKtide. We report inhibitory activity for the entire PLK family across a diverse set of small-molecule ATP-competitive inhibitors including several clinical compounds. With respect to both substrate and ATP-site specificity, highest similarity is observed between PLK2 and PLK3, PLK1 is next most similar, and PLK4 is least similar. Further, we have identified and report time-dependent inhibition by two potent and selective PLK inhibitors.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Johnson EF,Stewart KD,Woods KW,Giranda VL,Luo Ydoi
10.1021/bi7008745subject
Has Abstractpub_date
2007-08-21 00:00:00pages
9551-63issue
33eissn
0006-2960issn
1520-4995journal_volume
46pub_type
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