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The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity

Van Etten, Richard A. and Jackson, Peter K. and Baltimore, David and Sanders, Mitchell C. and Matsudaira, Paul T. and Janmey, Paul A. (1994) The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity. Journal of Cell Biology, 124 (3). pp. 325-340. ISSN 0021-9525. PMCID PMC2119935; PMC2119950. https://resolver.caltech.edu/CaltechAUTHORS:ETTjcb94

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Abstract

The myristoylated form of c-Abl protein, as well as the P210bcr/abl protein, have been shown by indirect immunofluorescence to associate with F-actin stress fibers in fibroblasts. Analysis of deletion mutants of c-Abl stably expressed in fibroblasts maps the domain responsible for this interaction to the extreme COOH-terminus of Abl. This domain mediates the association of a heterologous protein with F-actin filaments after microinjection into NIH 3T3 cells, and directly binds to F-actin in a cosedimentation assay. Microinjection and cosedimentation assays localize the actin-binding domain to a 58 amino acid region, including 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-rich region that mediates binding and sequestration of G-actin, and the Abl F- and G-actin binding domains cooperate to bundle F-actin filaments in vitro. The COOH terminus of Abl thus confers several novel localizing functions upon the protein, including actin binding, nuclear localization, and DNA binding. Abl may modify and receive signals from the F-actin cytoskeleton in vivo, and is an ideal candidate to mediate signal transduction from the cell surface and cytoskeleton to the nucleus.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1083/jcb.124.3.325DOIArticle
https://doi.org/10.1083/jcb.124.5.865DOICorrection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119935PubMed CentralArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119950PubMed CentralCorrection
ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 1994 by The Rockefeller University Press. Received for publication 9 August 1993 and in revised form 17 November 1993. We thank Dr. Michael Way for the gift of the cDNA expression construct of the gelsolin S2-3 domain, much helpful advice, and for reading the manuscript; Dr. Lloyd Klickstein for the gift of 125I-protein A; Mr. Sivarama Pokala for the gift of purified actin; and Dr. Lorraine Laham for electron microscopy. This work was supported in part by a grant from the Lucille P. Markey Charitable Trust to R.A. Van Etten, National Institutes of Health grant CA51462 to D. Baltimore, National Institutes of Health grant AR38910 to P.A. Janmey, and National Institutes of Health grant DK35306 to P.T. Matsudaira. R.A. Van Etten is a Lucille P. Markey Scholar in Biomedical Science. [published erratum appears in J Cell Biol 1994 Mar;124(5):865].
Errata:On page 338, in the second column, in the second full paragraph, there is an error in the second to last sentence. The protein discussed "has been shown to function as a GAP for" Rac, not Rho as printed.
Funders:
Funding AgencyGrant Number
Lucille P. Markey Charitable TrustUNSPECIFIED
NIHCA51462
NIHAR38910
NIHDK35306
Issue or Number:3
PubMed Central ID:PMC2119935; PMC2119950
Record Number:CaltechAUTHORS:ETTjcb94
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:ETTjcb94
Official Citation:RA Van Etten, PK Jackson, D Baltimore, MC Sanders, PT Matsudaira, PA Janmey; The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity. J Cell Biol 1 February 1994; 124 (3): 325–340. doi: https://doi.org/10.1083/jcb.124.3.325
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9563
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:04 Feb 2008
Last Modified:13 May 2020 17:45

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