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PMID: 2496972 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Deletion of an N-terminal regulatory domain of the c-abl tyrosine kinase activates its oncogenic potential.

The EMBO journal ·Vol. 8 ·No. 1 ·1989-01-00 ·Pages 137-47

Franz WM, Berger P, Wang JY

Abstract

The requirements for the oncogenic conversion of the c-abl proto-oncogene have been determined by the expression of N-terminal deleted forms and viral gag-fused forms of the c-abl proteins from a selectable retroviral vector. To activate the transforming potential of c-abl, it is necessary that (i) specific N-terminal amino acids are deleted to release the kinase from negative regulation in vivo; (ii) an N-terminal myristylation site is part of the activated kinase; (iii) the fatty-acylated, activated kinase is overproduced. The N-terminal amino acids found to be necessary for the cellular inhibition of c-abl tyrosine phosphorylation are part of a homologous region present in many non-receptor tyrosine kinases, the v-crk oncogene and phospholipase C-II. Overproduction of a deregulated and myristylated c-abl tyrosine kinase induces the transformation of NIH 3T3 cells.

MeSH Terms
Abelson murine leukemia virus/genetics Amino Acid Sequence Cell Line Cell Transformation, Neoplastic/enzymology Chromosome Deletion Enzyme Activation Fibroblasts Fusion Proteins, bcr-abl Gene Products, gag Moloney murine leukemia virus/genetics Neoplasm Proteins/physiology Phosphorylation Protein Processing, Post-Translational Protein-Tyrosine Kinases/genetics,metabolism Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-abl Recombinant Fusion Proteins/metabolism Retroviridae Proteins/genetics Viral Proteins/physiology
Chemicals
Gene Products, gag Neoplasm Proteins Proto-Oncogene Proteins Recombinant Fusion Proteins Retroviridae Proteins Viral Proteins Protein-Tyrosine Kinases Fusion Proteins, bcr-abl Proto-Oncogene Proteins c-abl
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Franz W M
Department of Biology, UCSD, La Jolla 92093.
Berger P
Wang J Y
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47 references, click to expand
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1989-01-00
Pages
137-47
Language
English
Region
England
NLM ID
8208664
PMCID
PMC400782
Subset
IM
Grants
NCI NIH HHS · R01 CA043054 · United States
NCI NIH HHS · CA 43054 · United States
External Links
PubMed source PMC Full Text View journal details
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