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cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases
G M Fox1, P L Holst, H T Chute
1Department of Immunology, Amgen, Inc., Thousand Oaks, California 91320-1789.
Abstract:
We have isolated cDNA clones from a human fetal brain library that encode five members of the EPH sub-family of receptor protein tyrosine kinases (PTKs). Comparison of the DNA sequences of these receptors to the Genbank database reveals that two of our clones correspond to the previously identified HEK and ERK receptors, two are apparently human homologues of the mouse receptors Sek and Bsk and one is novel. With these additions, the number of known human EPH sub-family members is nine and the total in all vertebrate species is 13 making it the largest known sub-family of PTKs. Analysis of the expression pattern of EPH sub-family mRNAs reveals that some are expressed in a wide variety of adult tissues while others are quite restricted. Consistent with the amplification of these sequences from a fetal brain cDNA library, all five members which we have isolated are expressed in the brain. We have named these receptors HEK4, HEK5, HEK7, HEK8 and HEK11, following the nomenclature of Wicks et al. (1992) and the numbering convention set forth by Sajjadi et al. (1991). Analysis of these new EPH sub-family members will increase our understanding of the biology of this receptor family and their isolation will provide reagents for the identification of ligands for this large family of orphan receptors.
Insights
Researchers identified five new human EPH receptor tyrosine kinase (RTK) genes in fetal brain tissue. This discovery expands the EPH family to 13 members in vertebrates, aiding the study of brain development and RTK signaling.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- The EPH family represents the largest known subfamily of protein tyrosine kinases (PTKs).
- Understanding the diversity and expression of EPH receptors is crucial for deciphering their roles in development and disease.
Purpose of the Study:
- To isolate and characterize novel members of the EPH receptor subfamily from a human fetal brain cDNA library.
- To expand the known repertoire of human EPH receptors and investigate their expression patterns.
Main Methods:
- cDNA library screening (human fetal brain).
- DNA sequence analysis and comparison with the Genbank database.
- Messenger RNA (mRNA) expression pattern analysis.
Main Results:
- Five novel EPH subfamily receptor PTKs were isolated and named HEK4, HEK5, HEK7, HEK8, and HEK11.
- Two clones were identified as human homologues of mouse Sek and Bsk, and two others as HEK and ERK.
- All five newly identified receptors are expressed in the human brain, with varying expression in other adult tissues.
Conclusions:
- The human EPH subfamily now comprises nine members, and the total vertebrate members reach 13, making it the largest PTK subfamily.
- These findings enhance our understanding of EPH receptor biology and provide essential tools for identifying their ligands.
- The brain-specific expression of these novel EPH receptors suggests critical roles in neural development and function.