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Chromosomal Mapping of Members of the cdc2 Family of Protein Kinases, cdk3, cdk6, PISSLRE, and PITALRE, and a cdk Inhibitor, p27^Kip1, to Regions Involved in Human Cancer¹

Jefferson Cancer Institute and Department of Microbiology and Immunology, Thomas Jefferson University [F. B., T. K. M., N. S., T. D., M. L. V., K. H., C. M. C., A. G.], Philadelphia, Pennsylvania 19107; North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030 [S. L. A., N. C.]; and Program in Molecular Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [A. K.]

Orderly progression through the cell cycle requires sequential activation and inactivation of cyclin-dependent kinases (cdks). This is achieved in part through the association of cdks with positive regulators called cyclins and inactivation of cyclin-cdk complexes by a rapidly growing number of cyclin-cdk inhibitors. Recently, the role of cell cycle control proteins both as primary effectors and as mediators of tumorigenesis has become a subject of increased interest. Here we report the chromosomal mapping of two cdks, cdk3 and cdk6, two putative cdks, PISSLRE and PITALRE, and one cyclin-dependent kinase inhibitor, p27, to chromosomal regions which may be altered in human tumors and examine their possible involvement in some of these malignancies. In particular, two of the kinases, cdk3 and PISSLRE and PITALRE, the cdc2-related kinases recently cloned by us, map to regions previously shown to exhibit loss of heterozygosity in breast and other tumors.

¹ This work was supported by NIH Grant R01 A1 10811 (N. C.), The Society of The Memorial Sloan-Kettering Cancer Center (A. K.), National Cancer Institute Grants CA39860 (C. M. C.) and R01 CA60999, The Council for Tobacco Research, and a grant from W. W. Smith Charitable Trusts (A. G.). F. B. is supported by the National Research Fellowship Award, National Cancer Institute 5 F31 CA60352-02. T. K. M. is supported by NIH Training Grant 1-T32-HL07780.

² To whom requests for reprints should be addressed, at Institute for Cancer Research and Molecular Medicine, Jefferson Cancer Institute, and Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107.

Received 11/29/94. Accepted 2/ 1/95.

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