@article{cd1127eaa0b6490fbf4d1a427ecc807e,
title = "Allosteric inhibition of the nonMyristoylated c-Abl tyrosine kinase by phosphopeptides derived from Abi1/Hssh3bp1",
abstract = "Here we report c-Abl kinase inhibition mediated by a phosphotyrosine located in trans in the c-Abl substrate, Abi1. The mechanism, which is pertinent to the nonmyristoylated c-Abl kinase, involves high affinity concurrent binding of the phosphotyrosine pY213 to the Abl SH2 domain and binding of a proximal PXXP motif to the Abl SH3 domain. Abi1 regulation of c-Abl in vivo appears to play a critical role, as demonstrated by inhibition of pY412 phosphorylation of the nonmyristoylated Abl by coexpression of Abi1. Pervanadate-induced c-Abl kinase activity was also reduced upon expression of the wild type Abi1 but not by expression of the Y213 to F213 mutant Abi1 in LNCaP cells, which are naturally deficient in the regulatory pY213. Our findings suggest a novel mechanism by which Abl kinase is regulated in cells.",
keywords = "Abi1, Allosteric mechanism, Hssh3bp1, SH3 and SH2 domain, Tyrosine kinase activity, c-Abl",
author = "Xiaoling Xiong and Ping Cui and Sajjad Hossain and Rong Xu and Brian Warner and Xinhua Guo and Xiuli An and Debnath, {Asim K.} and David Cowburn and Leszek Kotula",
note = "Funding Information: We thank B Mayer and T Koleske for the plasmids and for their helpful discussions; J Farmar for the help in protein analysis; S Heck for the help with flow cytometry; R Kascsak and J Chen for their assistance with Abi1/Hssh3bp1 monoclonal antibodies; J Xu for technical assistance; and E Luna, C Redman, and M Narla for helpful discussions. Supported by grants from Department of Defense Prostate Cancer Research Program (DAMD17-01-1-0096)(LK), NINDS (NS44968)(LK), NIGM (GM47021) (DC). S Hossain was supported by the FM Kirby Foundation, Inc., Morristown, NJ. The Voyager DE was purchased through funding from the Horace W. Goldsmith Foundation, (New York, NY) and the Hyde & Watson Foundation (Chatham Township, NJ). The Biacore 3000 was purchased through funding from the Abby R. Mauze Charitable Trust (New York, NY).",
year = "2008",
month = may,
doi = "10.1016/j.bbamcr.2008.01.028",
language = "English (US)",
volume = "1783",
pages = "737--747",
journal = "Biochimica et Biophysica Acta - Molecular Cell Research",
issn = "0167-4889",
publisher = "Elsevier",
number = "5",
}