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Isolation and oncogenic potential of a novel human src-like gene
Abstract:
We have isolated cDNA molecules representing the complete coding sequence of a new human gene which is a member of the src family of oncogenes. Nucleotide sequence analysis revealed that this gene, termed slk, encoded a 537-residue protein which was 86% identical to the chicken proto-oncogene product, p60c-src, over a stretch of 191 amino acids at its carboxy terminus. In contrast, only 6% amino acid homology was observed within the amino-terminal 82 amino acid residues of these two proteins. It was possible to activate slk as a transforming gene by substituting approximately two-thirds of the slk coding sequence for an analogous region of the v-fgr onc gene present in Gardner-Rasheed feline sarcoma virus. The resulting hybrid protein molecule expressed in transformed cells demonstrated protein kinase activity with specificity for tyrosine residues.
Insights
Researchers identified a new human gene, slk, belonging to the src family of oncogenes. This gene encodes a protein similar to chicken p60c-src and can be activated as a transforming gene, exhibiting tyrosine kinase activity.
Area of Science:
- Molecular Biology
- Oncogenes
- Signal Transduction
Background:
- The src family of oncogenes plays a crucial role in cellular signaling pathways.
- Identification of novel members of this family is essential for understanding cancer development.
Purpose of the Study:
- To isolate and characterize a new human gene within the src family of oncogenes.
- To investigate the transforming potential and enzymatic activity of the novel gene product.
Main Methods:
- cDNA isolation and sequencing
- Sequence homology analysis comparing human slk and chicken p60c-src
- Gene construct generation by substituting slk sequence into a feline sarcoma virus oncogene
- Expression of hybrid protein in transformed cells and assessment of protein kinase activity
Main Results:
- Isolation of a novel human src family gene, termed slk.
- The slk protein (537 residues) shows high homology (86%) to chicken p60c-src at the carboxy terminus but low homology (6%) at the amino terminus.
- Activation of slk as a transforming gene was achieved by creating a hybrid oncogene.
- The resulting hybrid protein demonstrated protein kinase activity specific for tyrosine residues.
Conclusions:
- The novel human gene slk is a member of the src family of oncogenes.
- The slk gene product possesses transforming capabilities and tyrosine kinase activity, suggesting its potential role in oncogenesis.
- Structural similarities and differences between slk and p60c-src provide insights into src family protein function.