BCR first exon sequences specifically activate the BCR/ABL tyrosine kinase oncogene of Philadelphia chromosome-positive human leukemias

Journal Article · Sun Mar 31 23:00:00 EST 1991 · Molecular and Cellular Biology; (United States)

DOI:https://doi.org/10.1128/MCB.11.4.1785· OSTI ID:7176830

Muller, A J; Witte, O N ^[1]; Young, J C; Pendergast, A; Pondel, M ^[2]; Landau, N R; Littman, D R ^[3]

---

1. Molecular Biology Institute, University of California, Los Angeles, (United States)
2. University of California, Los Angeles (United States)
3. University of California, San Francisco (United States)

The c-abl proto-oncogene encodes a cytoplasmic tyrosine kinase which is homologous to the src gene product in its kinase domain and in the upstream kinase regulatory domains SH2 (src homology region 2) and SH3 (src homology region 3). The murine v-abl oncogene product has lost the SH3 domain as a consequence of N-terminal fusion of gag sequences. Deletion of the SH3 domain is sufficient to render the murine c-abl proto-oncogene product transforming when myristylated N-terminal membrane localization sequences are also present. In contrast, the human BCR/ABL oncogene of the Philadelphia chromosome translocation has an intact SH3 domain and its product is not myristylated at the N terminus. To analyze the contribution of BCR-encoded sequences to BCR/ABL-mediated transformation, the effects of a series of deletions and substitutions were assessed in fibroblast and hematopoietic-cell transformation assays. BCR first-exon sequences specifically potentiate transformation and tyrosine kinase activation when they are fused to the second exon of otherwise intact c-ABL. This suggests that BCR-encoded sequences specifically interfere with negative regulation of the ABL-encoded tyrosine kinase, which would represent a novel mechanism for the activation of nonreceptor tyrosine kinase-encoding proto-oncogenes.

• OSTI ID: 7176830
• Journal Information: Molecular and Cellular Biology; (United States), Journal Name: Molecular and Cellular Biology; (United States) Vol. 11:4; ISSN 0270-7306; ISSN MCEBD4
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
CARBOXYLIC ACIDS
CHROMOSOMAL ABERRATIONS
CHROMOSOMES
CONNECTIVE TISSUE CELLS
DISEASES
DNA SEQUENCING
ENZYMES
FIBROBLASTS
GENES
HETEROCHROMOSOMES
HYDROXY ACIDS
IMMUNE SYSTEM DISEASES
LEUKEMIA
METABOLIC ACTIVATION
MUTATIONS
NEOPLASMS
ONCOGENES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHILADELPHIA CHROMOSOME
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROTEINS
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
TYROSINE