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Ctk: a protein-tyrosine kinase related to Csk that defines an enzyme family
1Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543.
Abstract:
We used the polymerase chain reaction with degenerate oligonucleotide primers to search for Csk-related kinases. A cDNA coding for a Csk-like protein-tyrosine kinase was cloned from mouse brain and was designated ctk, for csk-type protein-tyrosine kinase. The 1.9-kb ctk mRNA was found to be expressed predominantly in brain and capable of encoding a 52-kDa protein-tyrosine kinase. The amino acid sequence of Ctk was found to possess 53% identity with mouse Csk, shared all the predicted structural features of Csk, and was capable of phosphorylating the carboxyl-terminal conserved tyrosine of Src family members. Our results thereby indicate that ctk represents a gene that defines a family of structurally and functionally related Csk-like protein-tyrosine kinases.
Insights
Researchers discovered a novel protein-tyrosine kinase, ctk, in mouse brain. This Csk-like kinase is predominantly expressed in the brain and phosphorylates Src family members, suggesting a new kinase family.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- Csk (c-Src tyrosine kinase) plays a crucial role in regulating Src family kinases.
- The existence of other Csk-related kinases was hypothesized but not yet identified.
Purpose of the Study:
- To identify and characterize novel Csk-related protein-tyrosine kinases.
- To determine the functional and structural relationship of newly identified kinases to Csk.
Main Methods:
- Polymerase chain reaction (PCR) using degenerate oligonucleotide primers.
- cDNA cloning from mouse brain.
- mRNA expression analysis.
- Protein sequencing and functional assays.
Main Results:
- A novel Csk-like protein-tyrosine kinase, designated ctk, was cloned from mouse brain cDNA.
- ctk mRNA (1.9-kb) showed predominant expression in the brain, encoding a 52-kDa protein.
- Ctk shares 53% amino acid identity with mouse Csk and possesses similar structural features.
- Ctk demonstrated the ability to phosphorylate the C-terminal tyrosine of Src family members.
Conclusions:
- The gene ctk defines a new family of Csk-like protein-tyrosine kinases.
- These kinases are structurally and functionally related to Csk.
- ctk likely plays a significant role in regulating Src family kinase activity, particularly in the brain.