The nuclear tyrosine kinase c-Abl negatively regulates cell growth.

Abstract:

:c-Abl is a tyrosine kinase localized primarily in the nucleus. Previous assays for abl function rely on cellular transformation by abl mutants, which are cytoplasmic. Using a conditional overexpression strategy, we have developed a functional assay for c-abl. Overexpression of c-abl inhibits growth by causing cell cycle arrest. Growth suppression requires tyrosine kinase activity, nuclear localization, and an intact SH2 domain. Overexpression of dominant negative c-abl disrupts cell cycle control and enhances transformation by tyrosine kinases, G proteins, and transcription factor oncogenes. These findings suggest that c-abl acts as a negative regulator of cell growth. This growth suppressive activity is functionally similar to that of tumor suppressor genes such as p53 and Rb.

journal_name

Cell

journal_title

Cell

authors

Sawyers CL,McLaughlin J,Goga A,Havlik M,Witte O

doi

10.1016/0092-8674(94)90240-2

subject

Has Abstract

pub_date

1994-04-08 00:00:00

pages

121-31

issue

1

eissn

0092-8674

issn

1097-4172

pii

0092-8674(94)90240-2

journal_volume

77

pub_type

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