Growth inhibition by Abl requires an interplay of its SH2 and tyrosine kinase domains.
Overexpression of c-Abl tyrosine kinase can be growth inhibitory in certain fibroblast cell lines. Using a series of conditional chimeras between Abl and Src, we have now further dissected the Abl protein to determine which domains are required for this function. We found that growth inhibition, unlike transformation by oncogenic forms of Abl, is dependent on the presence of the cognate SH2 and tyrosine kinase domains. Since growth inhibition correlates with low tyrosine kinase activity, it may involve highly specific interactions of target proteins with both domains without the processivity of phosphorylation associated with oncogenic Abl.
Mattioni
T
T
Département de Biologie Cellulaire, Université de Genève, Switzerland.
Mayer
B J
BJ
Picard
D
D
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic; D006131:Growth Inhibitors / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D015394:Molecular Structure; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D016315:Proto-Oncogene Proteins c-abl / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D013329:Structure-Activity Relationship; D018909:src Homology Domains
D006131:Growth Inhibitors; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl