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PMID: 7739521 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Src activity increases and Yes activity decreases during mitosis of human colon carcinoma cells.

Molecular and cellular biology ·Vol. 15 ·No. 5 ·1995-05-00 ·Pages 2374-82

Park J, Cartwright CA

Abstract

Src and Yes protein-tyrosine kinase activities are elevated in malignant and premalignant tumors of the colon. To determine whether Src activity is elevated throughout the human colon carcinoma cell cycle as it is in polyomavirus middle T antigen- or F527 Src-transformed cells, and whether Yes activity, which is lower than that of Src in the carcinoma cells, is regulated differently, we measured their activities in cycling cells. We observed that the activities of both kinases were higher throughout all phases of the HT-29 colon carcinoma cell cycle than in corresponding phases of the fibroblast cycle. In addition, during mitosis of HT-29 cells, Src specific activity increased two- to threefold more, while Yes activity and abundance decreased threefold. The decreased steady-state protein levels of Yes during mitosis appeared to be due to both decreased synthesis and increased degradation of the protein. Inhibition of tyrosine but not serine/threonine phosphatases abolished the mitotic activation of Src. Mitotic Src was phosphorylated at novel serine and threonine sites and dephosphorylated at Tyr-527. Two cellular proteins (p160 and p180) were phosphorylated on tyrosine only during mitosis. Tyrosine phosphorylation of several other proteins decreased during mitosis. Thus, Src in HT-29 colon carcinoma cells, similar to Src complexed to polyomavirus middle T antigen or activated by mutation at Tyr-527, is highly active in all phases of the cell cycle. Moreover, Src activity further increases during mitosis, whereas Yes activity and abundance decrease. Thus, Src and Yes appear to be regulated differently during mitosis of HT-29 colon carcinoma cells.

MeSH Terms
Aphidicolin/pharmacology CSK Tyrosine-Protein Kinase Colonic Neoplasms/genetics,metabolism,pathology DNA Polymerase II/antagonists & inhibitors G2 Phase/genetics,physiology Humans Mitosis/drug effects,genetics,physiology Nocodazole/pharmacology Phosphoprotein Phosphatases/antagonists & inhibitors Phosphorylation Protein Tyrosine Phosphatases/antagonists & inhibitors Protein-Tyrosine Kinases/genetics,metabolism Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-yes Tumor Cells, Cultured src-Family Kinases
Chemicals
Proto-Oncogene Proteins Aphidicolin Protein-Tyrosine Kinases CSK Tyrosine-Protein Kinase Proto-Oncogene Proteins c-yes src-Family Kinases CSK protein, human DNA Polymerase II Phosphoprotein Phosphatases Protein Tyrosine Phosphatases Nocodazole
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Park J
Department of Medicine, Stanford University, California 94305, USA.
Cartwright C A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.15.5.2374
Published
1995-05-00
Pages
2374-82
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC230466
Subset
IM
Grants
NIDDK NIH HHS · R29 DK43743 · United States
External Links
PubMed source DOI: 10.1128/MCB.15.5.2374 PMC Full Text View journal details
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