Novel human oncogene lbc 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 repeat sequence as probe followed by cDNA cloning of this oncogene, termed lbc, was undertaken. The lbc cDNA sequence shows no identity to known 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 regulatory activity for the ras superfamily of small G proteins, while the C-terminus contains homology with pleckstrin and rac protein kinase in a region which overlaps with the recently defined PH (pleckstrin homology) domain. Lbc expression is restricted to human hematopoietic cells and skeletal muscle, lung and heart. Transfection of 3T3 cells with an expression vector encoding lbc cDNA results in focus formation, demonstrating its biological activity. These data indicate that the lbc oncogene encodes a novel product implicated in distinct cellular signal transduction functions.
Toksoz
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Department of Hematology/Oncology Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Williams
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DA
D016475:3T3 Cells; D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics; D015152:Blotting, Northern; D015139:Blotting, Southern; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D008168:Lung / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D009857:Oncogenes / Q000235:genetics*; D010750:Phosphoproteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D004273:DNA, Neoplasm; D015778:Minor Histocompatibility Antigens; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C039077:platelet protein P47; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt