However, the normal role of c-Abl remained unknown, despite studies in other laboratories that linked the homolog of c-Abl in fruit flies with the growth of nerve cells and the metabolic pathways governing formation and rearrangement of the cytoskeleton.

In their experiments, the Duke Medical Center researchers basically explored the effects of genetically manipulating mouse cells called fibroblasts to alter the levels of the growth factors and the protein enzymes produced by c-Abl and Src. Both these enzymes are chemical switches called tyrosine kinases, that trigger other proteins by adding a phosphate to the amino acid tyrosine that is part of the protein.

By altering levels of the growth factors and Src, in the mouse cells and observing the effects on c-Abl, the scientists could determine whether they were part of the normal pathway by which c-Abl functioned.

The pharmacologists' measurements revealed that the growth factors and the Src protein did trigger the activity of c-Abl protein. What's more, their studies revealed that the Src added phosphate to the c-Abl protein, the normal action of a kinase triggering another enzyme.

The scientists also found hints of another pathway by which the growth factors activate c-Abl without triggering Src.

Finally, they found that c-Abl was necessary for cells to undergo cytoskeletal reorganization in response to PDGF. For example, when fibroblast cells that lacked c-Abl were "starved" of serum and then the PDGF growth factor was added, they were unable to remodel their cytoskeleton, as revealed by microscopic studies. However, cells with c-
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Contact: Dennis Meredith
Dennis.meredith@duke.edu
919-681-8054
Duke University
28-Sep-1999