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. 1993 May;12(5):1947–1954. doi: 10.1002/j.1460-2075.1993.tb05844.x

A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes.

D S Peeper 1, L L Parker 1, M E Ewen 1, M Toebes 1, F L Hall 1, M Xu 1, A Zantema 1, A J van der Eb 1, H Piwnica-Worms 1
PMCID: PMC413416  PMID: 8491188

Abstract

Both cyclins A and B associate with and thereby activate cyclin-dependent protein kinases (cdks). We have investigated which component in the cyclin-cdk complex determines its substrate specificity. The A- and B-type cyclin-cdk complexes phosphorylated histone H1 and their cyclin subunits in an indistinguishable manner, irrespective of the catalytic subunit, p33cdk2 or p34cdc2. In contrast, only the cyclin A-cdk complexes phosphorylated the Rb-related p107 protein in vitro. Likewise, binding studies revealed that cyclin A-cdk complexes bound stably to p107 in vitro, whereas cyclin B-cdk complexes did not detectably associate with p107, under identical assay conditions. Binding to p107 required both cyclin A and a cdk as neither subunit alone bound to p107. These results demonstrate that although the kinase subunit provides a necessary component for binding, it is the cyclin subunit that plays the critical role in targeting the complex to p107. Finally, we show that the cyclin A-p33cdk2 complex phosphorylated p107 in vitro at most of its sites that are also phosphorylated in human cells, suggesting that the cyclin A-p33cdk2 complex is a major kinase for p107 in vivo.

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Selected References

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