Leukocytes express a novel gene encoding a putative transmembrane protein-kinase devoid of an extracellular domain

Tyrosine-specific phosphorylation of proteins is a key to the control of diverse pathways leading to cell growth and differentiation¹. The protein-tyrosine kinases described to date are either transmembrane proteins having an extracellular ligand binding domain^2-7 or cytoplasmic proteins related to the v-src oncogene^8-10. Most of these proteins are expressed in a wide variety of cells and tissues; few are tissue-specific¹. Previous studies have suggested that lymphokines could mediate haematopoietic cell survival through their action on glucose transport^11,12, regulated in some cells through the protein-tyrosine kinase activity of the insulin receptor¹³. We have investigated the possibility that insulin receptor-like genes are expressed specifically in haematopoietic cells. Using the insulin receptor-related avian sarcoma oncogene v-ros as a probe¹⁴, we have isolated and characterized the complementary DNA of a novel gene, ltk (leukocyte tyrosine kinase). The ltk gene is expressed mainly in leukocytes, is related to several tyrosine kinase receptor genes of the insulin receptor family and has unique structural properties: it apparently encodes a transmembrane protein devoid of an extracellular domain. Two candidate ltk proteins have been identified with antibodies in the mouse thymus, and have properties indicating that they are integral membrane proteins. These features suggest that ltk could be a signal transduction subunit for one or several of the haematopoietic receptors.