A novel Yes-related kinase, Yrk, is expressed at elevated levels in neural and hematopoietic tissues.

While screening a chicken kidney cDNA library for the normal homolog of the yes oncogene, we isolated a clone that encodes a novel non-receptor type protein tyrosine kinase of the Src family. We named this gene product Yrk (York), as an acronym for Yes-related kinase. As predicted from the cDNA sequence, the Yrk protein consists of 536 amino acids and has all the canonical features of a Src kinase. At the amino terminus it contains a myristylation signal, followed by a unique domain, SH3 and SH2 motifs, an ATP binding site, a kinase region and a carboxy-terminal sequence with a potential regulatory tyrosine at position 530. The sequence of the Yrk protein showed 79% identity with human Fyn and 72% identity with chicken Yes. To eliminate the possibility that the Yrk protein is an avian homolog of mammalian Fyn, we isolated and sequenced the chicken fyn cDNA. The sequence data together with Southern and Northern blot analyses showed that the chicken yrk gene is distinct from the chicken fyn gene. Antibodies generated against the unique domain of the yrk protein expressed in bacteria precipitated a 60-kDa protein that was active in an immune complex kinase assay and was phosphorylated on tyrosine. Expression of the Yrk protein in adult chicken tissues was elevated in cerebellum and spleen. Relatively high levels of Yrk were also found in lung and skin.