Tyrosine protein kinase activity of the HZ4-feline sarcoma virus P80gag-kit-transforming protein
Related Experiment Video
Updated: Oct 22, 2026
Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
1Molecular Biology Program, Sloan Kettering Institute, New York, New York.
Abstract:
The Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV), isolated from a feline fibrosarcoma, is a replication defective acute transforming feline retrovirus that originated by transduction of feline c-kit sequences with feline leukemia virus (FeLV). The v-kit sequences of the HZ4-FeSV, a segment of 1106 nucleotides, correspond to sequences of the cytoplasmic domain of the c-kit receptor kinase. The HZ4-FeSV is known to encode an 80-kilodalton protein with FeLV gag and kit determinants. The P80gag-kit protein and its associated activities from HZ4-FeSV-transformed mink cells were characterized. The P80gag-kit protein was found to be myristoylated, suggesting a membrane association for this protein. In agreement with the predicted relationship with tyrosine kinases, by using the in vitro immune complex-kinase procedure, the P80gag-kit protein was shown to display a tyrosine-specific autophosphorylation activity. In vivo, the P80 protein was found to be phosphorylated on serine and threonine and to a lesser degree on tyrosine. In addition, potential in vivo protein substrates for tyrosine-specific phosphorylation mediated by the P80gag-kit kinase were identified in HZ4-FeSV-transformed cells.
Insights
The Hardy-Zuckerman 4 feline sarcoma virus encodes an 80-kilodalton protein (P80gag-kit) that exhibits tyrosine kinase activity. This protein is myristoylated, associated with the cell membrane, and phosphorylates other proteins in feline sarcoma virus-transformed cells.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- The Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV) is a defective retrovirus derived from feline leukemia virus (FeLV) and feline c-kit.
- HZ4-FeSV transduces feline c-kit sequences, resulting in a viral oncogene (v-kit).
Purpose of the Study:
- To characterize the P80gag-kit protein encoded by HZ4-FeSV.
- To investigate the biochemical activities and cellular localization of P80gag-kit in transformed cells.
Main Methods:
- Myristoylation analysis
- Immune complex-kinase assays
- In vivo phosphorylation studies
- Identification of in vivo protein substrates
Main Results:
- The P80gag-kit protein is myristoylated, indicating membrane association.
- P80gag-kit exhibits in vitro tyrosine-specific autophosphorylation activity.
- In vivo, P80gag-kit is phosphorylated on serine, threonine, and tyrosine residues.
- Potential in vivo substrates for P80gag-kit-mediated tyrosine phosphorylation were identified.
Conclusions:
- The P80gag-kit oncoprotein possesses intrinsic tyrosine kinase activity.
- Myristoylation and phosphorylation contribute to the function and regulation of P80gag-kit.
- HZ4-FeSV-transformed cells contain substrates phosphorylated by the P80gag-kit kinase, suggesting its role in transformation.
