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PMID: 3352600 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Neoplastic transformation induced by an activated lymphocyte-specific protein tyrosine kinase (pp56lck).

Molecular and cellular biology ·Vol. 8 ·No. 2 ·1988-02-00 ·Pages 540-50

Marth JD, Cooper JA, King CS, Ziegler SF, Tinker DA, Overell RW, Krebs EG, Perlmutter RM

Abstract

The lck proto-oncogene encodes a lymphocyte-specific member of the src family of protein tyrosine kinases. Here we demonstrate that pp56lck is phosphorylated in vivo at a carboxy-terminal tyrosine residue (Tyr-505) analogous to Tyr-527 of pp60c-src. Substitution of phenylalanine for tyrosine at this position resulted in increased phosphorylation of a second tyrosine residue (Tyr-394) and was associated with an increase in apparent kinase activity. In addition, this single point mutation unmasked the oncogenic potential of pp56lck in NIH 3T3 cell transformation assays. Viewed in the context of similar results obtained with pp60c-src, it is likely that the enzymatic activity and transforming ability of all src-family protein tyrosine kinases can be regulated by carboxy-terminal tyrosine phosphorylation. We further demonstrate that overexpression of pp56lck in the murine T-cell lymphoma LSTRA as a result of a retroviral insertion event produces a kinase protein that despite wild-type primary structure is nevertheless hypophosphorylated at Tyr-505. Thus, control of normal growth in this lymphoid cell line may have been abrogated through acquisition of a posttranslationally activated version of pp56lck.

MeSH Terms
Animals Cell Line Cell Transformation, Neoplastic Cells, Cultured Lymphocyte Activation Lymphocytes/enzymology,immunology Mice Mutation Phosphoproteins/analysis Phosphorylation Protein-Tyrosine Kinases/genetics,metabolism Proto-Oncogenes Retroviridae/genetics Transcription, Genetic Transfection
Chemicals
Phosphoproteins Protein-Tyrosine Kinases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Marth J D
Howard Hughes Medical Institute, Seattle, Washington.
Cooper J A
King C S
Ziegler S F
Tinker D A
Overell R W
Krebs E G
Perlmutter R M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.8.2.540-550.1988
Published
1988-02-00
Pages
540-50
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC363178
Subset
IM
Grants
NCI NIH HHS · CA41072 · United States
External Links
PubMed source DOI: 10.1128/mcb.8.2.540-550.1988 PMC Full Text View journal details
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