Transformation by Abelson Murine Leukemia Virus

Witte, Owen N.

Abstract

This proposal will investigate the molecular mechanisms involved in the abnormal growth regulation of murine lymphocytes transformed by the Abelson murine leukemia virus (A-MuLV). A detailed evaluation of the genetic and enzymatic properties of the A-MuLV transforming gene and its normal cellular homolog will be carried out. Preparation of improved serological and kinase substrate reagents will be done using synthetic peptide technology. Both wild type and mutants including partial or complete transformation defective strains, non-lethal variants, and temperature sensitive strains will be used to study the interaction of the viral phosphotyrosine kinase with the host cell environment. The temporal process and phenotypic progression of normal B lymphoid cells post-infection with A-MuLV towards the transformed state will be followed using newly developed cell culture techniques (Whitlock and Witte, 1982a). These studies will better define the nature of the A-MuLV target cell and cellular factors required for full expression of the transformed state in lymphoid cells.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Cancer Institute (NCI)
• Type: Research Project (R01)
• Project #: 5R01CA027507-06
• Application #: 3167664
• Study Section: Experimental Virology Study Section (EVR)
• Project Start: 1980-05-01
• Project End: 1986-04-30
• Budget Start: 1985-05-01
• Budget End: 1986-04-30
• Support Year: 6
• Fiscal Year: 1985

Institution

• Name: University of California Los Angeles
• Type: Schools of Arts and Sciences
• DUNS #: 119132785
• City: Los Angeles
• State: CA
• Country: United States
• Zip Code: 90095

Publications

Maru, Y; Witte, O N (1991) The BCR gene encodes a novel serine/threonine kinase activity within a single exon. Cell 67:459-68

Kelliher, M; Knott, A; McLaughlin, J et al. (1991) Differences in oncogenic potency but not target cell specificity distinguish the two forms of the BCR/ABL oncogene. Mol Cell Biol 11:4710-6

Parham, D M; Kelly, D R; Donnelly, W H et al. (1991) Immunohistochemical and ultrastructural spectrum of hepatic sarcomas of childhood: evidence for a common histogenesis. Mod Pathol 4:648-53

Kelliher, M A; McLaughlin, J; Witte, O N et al. (1990) Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci U S A 87:6649-53

Ponzetto, C; Wadewitz, A G; Pendergast, A M et al. (1989) P150c-abl is detected in mouse male germ cells by an in vitro kinase assay and is associated with stage-specific phosphoproteins in haploid cells. Oncogene 4:685-90

Daley, G Q; McLaughlin, J; Witte, O N et al. (1987) The CML-specific P210 bcr/abl protein, unlike v-abl, does not transform NIH/3T3 fibroblasts. Science 237:532-5

Konopka, J B; Watanabe, S M; Singer, J W et al. (1985) Cell lines and clinical isolates derived from Ph1-positive chronic myelogenous leukemia patients express c-abl proteins with a common structural alteration. Proc Natl Acad Sci U S A 82:1810-4