The nuclear tyrosine kinase c-Abl negatively regulates cell growth.
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.
Sawyers
C L
CL
Department of Medicine, University of California, Los Angeles 90024.
McLaughlin
J
J
Goga
A
A
Havlik
M
M
Witte
O
O
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle; D002467:Cell Nucleus / Q000201:enzymology*; D002471:Cell Transformation, Neoplastic; D015870:Gene Expression; D005799:Genes, Dominant; D016313:Genes, abl; D006131:Growth Inhibitors; D051379:Mice; D009857:Oncogenes; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D006131:Growth Inhibitors; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl