By screening a human fetal brain cDNA expression library using a monoclonal antiphosphotyrosine antibody and by 5' RACE procedures, we have isolated overlapping cDNAs encoding a receptor-type tyrosine kinase belonging to the EPH family, DRT (Developmentally Regulated EPH-related Tyrosine kinase gene). The DRT gene is expressed in three different size transcripts (i.e. 4, 5 and 11 kb). DRT transcripts are expressed in human brain and several other tissues, including heart, lung, kidney, placenta, pancreas, liver and skeletal muscle, but the 11 kb DRT transcript is preferentially expressed in fetal brain. Steady-state levels of DRT mRNA in several tissues, including brain, heart, lung and kidney, are greater in the midterm fetus than those in the adult. DRT transcripts are detectable at low levels in a human teratocarcinoma cell line (NTera-2), but its expression is greatly increased after the NTera-2 cells are induced to become postmitotic neurons (NTera-2N) by retinoic acid treatment. These data suggest that DRT plays a part in human neurogenesis. A large number of tumor cell lines derived from neuroectoderm express DRT transcripts, including 12 neuroblastomas, two medulloblastomas, one primitive neuroectodermal tumor and six small cell lung carcinomas (SCLC). Interestingly, several neuroblastoma cell lines with 1p deletion and one SCLC cell line express DRT transcripts of aberrant size (i.e. 3, 6 and 8 kb) in addition to those found in normal tissues. We mapped the DRT gene to human chromosome 1p35-1p36.1 by PCR screening of human-rodent somatic cell hybrid panels and by fluorescence in situ hybridization. As the distal end of chromosome 1p is often deleted in neuroblastomas and altered in some cases in SCLCs, these chromosomal abnormalities may have resulted in the generation of aberrant size transcripts. Thus, the DRT gene may play a part in neuroblastoma and SCLC tumorigenesis.
Amino Acid Sequence Animals