A functional screen for regulators of the c-Abl protein tyrosine kinase.

摘要: Abstract c-Abl protein tyrosine kinase activity is tightly regulated in vertebrate cells. Several mutations can activate Abl and convert it into an oncogene. In man, chromosomal translocations result in fusion proteins associated with chronic myelogenous leukemias and some acute lymphocytic leukemias. In viral forms of abl, gag sequences are fused to Abl portions resulting in a deletion of N-terminal sequences. To study c-Abl activity in a cellular environment likely to lack specific regulators, we have expressed human c-Abl in Schizosztccharomyces pombe in an inducible fashion, c-AN causes growth arrest followed by death of the cells. Mutations in the SH2 domain or in the autophosphorylation site dramatically reduce the ability of Abl to confer the growth arrest phenotype and to phosphorylate endogenous proteins, suggesting a fundamental role of these structures in the activity of the enzyme. An SH3 domain …