Translational regulation of the lymphocyte-specific protein tyrosine kinase p56lck

The lck gene encodes a lymphocyte-specific membrane-associated protein tyrosine kinase that is implicated in signal transduction processes that regulate T-cell growth. Previous studies demonstrate that lck transcripts, unlike most other vertebrate mRNAs, contain 5' proximal AUG sequences upstream relative to the major open reading frame (5' AUGs) that serve as satisfactory targets for recognition by 40S ribosomal subunits. There exist two distinct lck transcripts, generated through alternative promoter utilization, that differ only in their 5' untranslated region sequences. Both transcripts are present in murine and human lymphocytes, and the structures of the two distinct 5' untranslated regions have been closely conserved since the divergence of these species. Moreover, both transcripts contain 5'-AUG elements. Intriguingly, inspection of primary sequence data for other src-family transcripts reveals that virtually all contain 5'AUG triplets, and many contain a large number of these potential initiators. By analogy with the well-studied translational regulation of the yeast GCN4 gene, I propose that control of ribosomal reinitiation permits tight regulation of expression of the lck gene product and of other src-like protein tyrosine kinases.