HUMAN NEURAL TISSUES EXPRESS A TRUNCATED ROR1 RECEPTOR TYROSINE KINASE, LACKING BOTH EXTRACELLULAR AND TRANSMEMBRANE DOMAINS

Human heart, lung and kidney express a 6 kb mRNA encoding Ror1, a memb er of the receptor tyrosine kinase (RTK) family with as yet unknown li gand specificity. We used a Ror1 cDNA probe to screen a cDNA library p repared from the human neuronogenic teratocarcinoma line, NTera2, and cloned a 2373 nucleotide transcript, This transcript contains an open reading frame that encodes a 388 amino acid protein identical with the cytosolic, C-terminal region of ror1 but lacking the ror1 transmembra ne and entire extracellular domains, Northern blots demonstrate that m RNA encoding this truncated Ror1 ('t-Ror1') is abundantly expressed in fetal and adult human CNS, in human leukemia, lymphoma cell. lines, a nd in a variety of human cancers derived from neuroectoderm. While pre vious studies have documented alternative splicing patterns within 5' and 3' regions of mRNAs encoding various RTKs altering their ligand bi nding specificity or their intracellular signaling, the present report is the first to demonstrate tissue-specific alternative mRNA splicing causing loss of the entire extracellular and transmembrane regions of an RTK.