By screening a human fetal brain cDNA expression library using a monoclonal anti-phosphotyrosine antibody, we have isolated a cDNA clone encoding a receptor type protein-tyrosine kinase belonging to theEPHfamily,NET(neuronally expressedEPH-related tyrosine kinase).NETshows 87% homology in nucleotide sequence and 99% homology in the deduced amino acid sequence to ratelk,suggesting thatNETis the human homologue ofelk.TheNETgene is mapped to human chromosome 3q21-q23 by PCR screening of a human-rodent somatic cell hybrid panel and by fluorescencein situhybridization. Examination ofNETmRNA expression in several human tissues has shown that theNETgene is expressed preferentially in brain as a 5-kb transcript. Steady-state levels ofNETmRNA in human brain are greater in the midterm fetus than in the adult. Lower levels ofNETmRNA are found in fetal kidney and adult skeletal muscle. The expression pattern ofNETmRNA thus differs from that ofelk,suggesting that these two gene products may perform distinct roles in human and rat.NETtranscripts are detected in human NTera-2 teratocarcinoma cells after retinoic acid-induced neuronal differentiation. Several human tumor cell lines derived from neuroectoderm including primitive neuroectodermal tumor, small cell lung carcinoma, and neuroblastoma also expressNETtranscripts. Since theNETmRNA expression in human brain is developmentally regulated and is induced during neuronal differentiation,NETpotentially plays important roles in human neurogenesis.
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