The Molecular Perspective: c-Abl Tyrosine Kinase

Abstract

The Oncologist 2005;10:758–759 www.TheOncologist.com Correspondence: David S. Goodsell, Ph.D., Associate Professor, The Scripps Research Institute, Department of Molecular Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Telephone: 858-784-2839; Fax: 858-784-2860; e-mail: goodsell@scripps.edu; Website: http://www.scripps.edu/pub/goodsell Received August 18, 2005; accepted for publication August 18, 2005. ©AlphaMed Press 10837159/2005/$12.00/0 Phosphate groups are widely used for transmitting signals inside cells. Phosphate has a number of advantages in molecular signaling. With its strong charge and numerous opportunities for hydrogen bonding, it is particularly easy to recognize. Phosphate groups are also readily added to and removed from signaling molecules, using the cell’s ready supply of ATP to power the process. Phosphate groups may be added to small molecules to create characteristic molecules like cyclic AMP. They may also be added to proteins, changing their surface features or even modulating the activity of an enzyme. As you can imagine, however, one phosphate group looks much like every other one. To be useful in signaling, the phosphate groups must be attached in the proper place and at the proper time. To perform this function, our cells have more than 500 different protein kinases, each designed to add phosphates to a different set of proteins. These many kinases are involved in a complex, interconnected network of signaling, requiring careful control so that each kinase is activated only when its particular signal is needed. The c-Abl tyrosine kinase, shown in Figure 1, transmits messages about the adhesion of cells to their neighbors and messages indicating when it is time to grow or move to a new location. Like other members of the src family of protein kinases, c-Abl uses a complex conformational change to turn its kinase activity on and off. It is comprised of several domains connected by flexible linkers, including two small regulatory domains, a larger kinase domain, and several additional domains that bind to DNA and actin. In the inactive form, the protein folds into Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com CME The Molecular Perspective: c-Abl Tyrosine Kinase