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Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation

Baskaran, R. and Wood, L. D. and Whitaker, L. L. and Canman, C. E. and Morgan, S. E. and Xu, Y. and Barlow, C. and Baltimore, D. and Wynshaw-Boris, A. and Kastan, M. B. and Wang, J. Y. J. (1997) Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature, 387 (6632). pp. 516-519. ISSN 0028-0836. https://resolver.caltech.edu/CaltechAUTHORS:20200422-151000038

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Abstract

Ataxia telangiectasia (AT) is a rare human autosomal recessive disorder with pleiotropic phenotypes, including neuronal degeneration, immune dysfunction, premature ageing and increased cancer risk. The gene mutated in AT, ATM, encodes a putative lipid or protein kinase. Most of the human AT patient phenotypes are recapitulated in Atm-deficient mice. Cells derived from Atm^(-/-) mice, like those from AT patients, exhibit abnormal response to ionizing radiation. One of the known responses to ionizing radiation is the activation of a nuclear tyrosine kinase encoded by the c-abl/proto-oncogene. Ionizing radiation does not activate c-Abl in cells from AT patients or in thymocytes or fibroblasts from the Atm-deficient mice. Ectopic expression of a functional ATM kinase domain corrects this defect, as it phosphorylates the c-Abl tyrosine kinase in vitro at Ser 465, leading to the activation of c-Abl. A mutant c-Abl with Ser 465 changed to Ala 465 is not activated by ionizing radiation or ATM kinase in vivo. These findings identify the c-Abl tyrosine kinase as a downstream target of phosphorylation and activation by the ATM kinase in the cellular response to ionizing radiation.


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https://doi.org/10.1038/387516a0DOIArticle
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ORCID:
AuthorORCID
Baltimore, D.0000-0001-8723-8190
Additional Information:© 1997 MacMillan Publishing Group. Received 13 January; accepted 18 April 1997. This work was mainly supported by grants to J.Y.J.W. and a grant from the Council for Tobacco Research.
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Council for Tobacco ResearchUNSPECIFIED
Issue or Number:6632
Record Number:CaltechAUTHORS:20200422-151000038
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200422-151000038
Official Citation:Baskaran, R., Wood, L., Whitaker, L. et al. Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. Nature 387, 516–519 (1997). https://doi.org/10.1038/387516a0
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102735
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:23 Apr 2020 15:01
Last Modified:23 Apr 2020 15:01

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