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Nonmyristoylated Abl proteins transform a factor-dependent hematopoietic cell line

Daley, George Q. and Van Etten, Richard A. and Jackson, Peter K. and Bernards, Andre and Baltimore, David (1992) Nonmyristoylated Abl proteins transform a factor-dependent hematopoietic cell line. Molecular and Cellular Biology, 12 (4). pp. 1864-1871. ISSN 0270-7306. http://resolver.caltech.edu/CaltechAUTHORS:DALmcb92

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Abstract

N-terminal myristoylation can promote the association of proteins with the plasma membrane, a property that is required for oncogenic variants of Src and Abl to transform fibroblastic cell types. The P210bcr/abl protein of chronic myelogenous leukemia cells is not myristoylated and does not stably transform NIH 3T3 fibroblasts; however, it will transform lymphoid and myeloid cell types in vitro and in vivo, suggesting that myristoylation is not required for Abl variants to transform hematopoietic cells. To test this hypothesis, we introduced point mutations that disrupt myristoylation into two activated Abl proteins, v-Abl and a deletion mutant of c-Abl (delta XB), and examined their ability to transform an interleukin-3-dependent lymphoblastoid cell line, Ba/F3. Neither of the nonmyristoylated Abl proteins transformed NIH 3T3 fibroblasts, but like P210bcr/abl, both were capable of transforming the Ba/F3 cells to factor independence and tumorigenicity. Nonmyristoylated Abl variants did not associate with the plasma membrane in the transformed Ba/F3 cells. These results demonstrate that Abl proteins can transform hematopoietic cells in the absence of membrane association and suggest that distinct functions of Abl are required for transformation of fibroblast and hematopoietic cell types.


Item Type:Article
Additional Information:Copyright © 1992 by the American Society for Microbiology. Received 7 November 1991/Accepted 15 January 1992 This work was funded in part by NIH grant CA51462-02 and by a grant from the Lucille P. Markey Charitable Trust to R.A.V.
Record Number:CaltechAUTHORS:DALmcb92
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:DALmcb92
Alternative URL:http://mcb.asm.org/cgi/content/abstract/12/4/1864
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6989
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:04 Jan 2007
Last Modified:26 Dec 2012 09:27

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