NOVEL HUMAN ONCOGENE IBC DETECTED BY TRANSFECTION WITH DISTINCT HOMOLOGY REGIONS TO SIGNAL-TRANSDUCTION PRODUCTS

In order to isolate transforming genes involved in leukemias, DNA from a CML acute phase sample was transfected into NIH-3T3 Cells and found to be tumorigenic in nude mice. Partial genomic cloning using human r epeat sequence as probe followed by cDNA cloning of this oncogene, ter med Ibc, was undertaken. The lbc cDNA sequence shows no identity to kn own proteins and codes for a predicted hydrophilic protein product of 47 kD, which contains several consensus kinase phosphorylation sites. The N-terminus encodes a consensus E-F hand motif followed by a region of homology to the transforming human oncogene dbl associated with re gulatory activity for the ras superfamily of small G proteins, while t he C-terminus contains homology with pleckstrin and rac protein kinase in a region which overlaps with the recently defined PH (pleckstrin h omology) domain. Lbc expression is restricted to human hematopoietic c ells and skeletal muscle, lung and heart. Transfection of 3T3 cells wi th an expression vector encoding lbc cDNA results in focus formation, demonstrating its biological activity. These data indicate that the lb c oncogene encodes a novel product implicated in distinct cellular sig nal transduction functions.