MOLECULAR-CLONING OF TRKE, A NOVEL TRK-RELATED PUTATIVE TYROSINE KINASE RECEPTOR ISOLATED FROM NORMAL HUMAN KERATINOCYTES AND WIDELY EXPRESSED BY NORMAL HUMAN TISSUES

We have identified and cloned a new member of the trk gene family, ter med trkE, which generates a 3.9-kilobase (kb) transcript in normal hum an keratinocytes and in a variety of normal human tissues, but not in liver. Albeit at low level, trkE transcript is expressed also by PC12 cells. The open reading frame codes for a polypeptide of 876 amino aci ds exhibiting the classic features of cell surface tyrosine protein ki nases. trkE catalytic domain is 41% identical to trkA and shows severa l features unique to the trk gene family. Its extracellular domain doe s not show significant homology to any known proteins. trkE is the fir st member of this gene family found abundantly and widely expressed in normal human tissues. Several lines of evidence suggest that NGF is a lso the ligand for trkE; (i) normal human keratinocytes bind NGF with high affinity, (ii) NGF stimulates keratinocyte growth in an autocrine fashion, (iii) NGF exerts its biological effect on keratinocytes thro ugh the stimulation of a trk-specific tyrosine kinase, and (iv) kerati nocytes lack trkA but do express large amount of trkE. trkE might also be the NGF receptor by other human peripheral tissues, such as pancre atic islets, and might represent a non-neuronal receptor for this liga nd.