The ltk gene encodes a novel receptor-type protein tyrosine kinase.

Previously, analysis of cDNAs encoding the ltk tyrosine kinase suggested that the structure of this protein was unique among tyrosine kinases, containing a transmembrane domain but only a short, or virtually non-existent, extracellular domain. Further, it was suggested that translational initiation might occur predominantly at a CTG codon. We have now cloned and sequenced a putative full length human ltk cDNA which contains novel sequence information relative to previously identified cDNAs. This ltk cDNA encodes a protein product containing all of the features of typical receptor-type protein tyrosine kinase, including: an ATG translational initiation codon, a secretory signal sequence and a 347 amino acid extracellular domain as well as transmembrane and intracellular kinase domains. Ribonuclease protection analysis indicates that our cloned cDNA represents the most abundant species of mature ltk mRNA. In vitro transcription and translation of the ltk cDNA yields a 100 kDa protein, consistent with initiation at the putative ATG translational codon. In addition, transfection of the ltk cDNA into COS-1 cells produces a similar-sized, glycosylated protein possessing in vitro kinase activity. These data indicate that the ltk gene product likely functions as a cell surface receptor for an unidentified cellular growth factor.