Transcriptional Activation of a ras-Like Gene (kir) by Oncogenic Tyrosine Kinases

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 26; pp. 12448 - 12452
• Main Authors: Cohen, Lucie, Mohr, Randolph, Chen, Yunn-Yi, Huang, Mary, Kato, Roberta, Dorin, Dominique, Tamanoi, Fuyuhiko, Goga, Andrei, Afar, Daniel, Rosenberg, Naomi, Witte, Owen
• Format: Journal Article
• Language: English
• Published: United States National Academy of the Sciences of the United States of America 20.12.1994; National Acad Sciences; National Academy of Sciences
• Subjects: 3T3 Cells; Amino Acid Sequence; Animals; Biochemistry; Cell growth; Cell lines; Cell Transformation, Neoplastic; Cloning, Molecular; Complementary DNA; DNA, Complementary - genetics; Fusion Proteins, bcr-abl - metabolism; Gene Expression Regulation, Neoplastic; Genetics; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Lymphocytes; Messenger RNA; Mice; Molecular Sequence Data; Monomeric GTP-Binding Proteins; Myeloid cells; Oncogene Proteins v-abl - metabolism; Protein-Tyrosine Kinases - metabolism; Proteins; RNA; RNA, Messenger - genetics; Sequence Alignment; Sequence Homology, Amino Acid; Signal Transduction; Transcription, Genetic; Transformed cell line
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.26.12448

We report the characterization of a member of the ras gene family that is overexpressed in cells transformed by abl tyrosine kinase oncogenes. The gene, named kir (for kinase-inducible ras-like), is induced at the transcriptional level. kir mRNA has a rapid turnover and encodes a protein of 33 kDa with guanine nucleotide-binding activity but undetectable intrinsic GTPase activity. kir was cloned by differential screening of genes present in fully malignant versus growth factor-independent cell lines expressing wild-type or mutant forms of BCR/ABL. BCR/ABL and v-Abl induce transcription of the kir gene via specific signaling pathway(s), but kir overexpression alone is not sufficient to mediate transformation.