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The Nuclear Tyrosine Kinase Rak Associates with the Retinoblastoma Protein pRb¹

Curriculum in Genetics and Molecular Biology [R. J. C., E. T. L.], Lineberger Comprehensive Cancer Center [R. J. C., W. G. C., E. T. L.], Departments of Surgery [R. J. C., W. G. C.] and Medicine, Biochemistry and Biophysics [E. T. L.], University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599

Rak is a nuclear tyrosine kinase containing Src homology 2 and 3 domains at its NH₂ terminus. We report here that the retinoblastoma tumor susceptibility gene product pRb associates with Rak in vivo and in vitro. Rak binds to the A/B pocket region of pRb, a region that is frequently mutated in human cancer, during the G₁ and S phases of the cell cycle. Furthermore, Rak expression is elevated in G₁, and transfection of Rak into NIH 3T3 cells results in a significant decrease in the number of emerging colonies. Thus, Rak is a tyrosine kinase with growth suppressing activity that may function, in part, through its interaction with pRb.

¹ This work was supported by National Cancer Institute Grants CA58233-03 and CA01625. W. G. C. is a recipient of the George H. A. Clowes, Jr. Memorial Research Career Development Award from the American College of Surgeons. E. T. L. is a scholar of the American Leukemia Society.

² To whom requests for reprints should be addressed, at University of North Carolina at Chapel Hill, Room 237, Lineberger Comprehensive Cancer Center. CB# 7295, Chapel Hill, NC 27599.

Received 8/ 4/95. Accepted 8/15/95.

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