THE COOH TERMINUS OF THE C-ABL TYROSINE KINASE CONTAINS DISTINCT F-ACTIN AND G-ACTIN BINDING DOMAINS WITH BUNDLING ACTIVITY

The myristoylated form of c-Abl protein, as well as the P210bcr/abl pr otein, have been shown by indirect immunofluorescence to associate wit h F-actin stress fibers in fibroblasts. Analysis of deletion mutants o f c-Abl stably expressed in fibroblasts maps the domain responsible fo r this interaction to the extreme COOH-terminus of Abl. This domain me diates the association of a heterologous protein with F-actin filament s after microinjection into NIH 3T3 cells, and directly binds to F-act in in a cosedimentation assay. Microinjection and cosedimentation assa ys localize the actin-binding domain to a 58 amino acid region, includ ing a charged motif at the extreme COOH-terminus that is important for efficient binding. F-actin binding by Abl is calcium independent, and Abl competes with gelsolin for binding to F-actin. In addition to the F-actin binding domain, the COOH-terminus of Abl contains a proline-r ich region that mediates binding and sequestration of G-actin, and the Abl F- and G-actin binding domains cooperate to bundle F-actin filame nts in vitro. The COOH terminus of Abl thus confers several novel loca lizing functions upon the protein, including actin binding, nuclear lo calization, and DNA binding. Abl may modify and receive signals from t he F-actin cytoskeleton in vivo, and is an ideal candidate to mediate signal transduction from the cell surface and cytoskeleton to the nucl eus.