ASSOCIATION OF THE PROTEIN-KINASES C-BCR AND BCR-ABL WITH PROTEINS OFTHE 14-3-3-FAMILY

In this study, a protein that interacts with sequences encoded by the first exon of the protein kinase Bcr was cloned. The Bcr-associated pr otein 1 (Bap-1) is a member of the 14-3-3 family of proteins. Bap-1 in teracts with full-length c-Bcr and with the chimeric Bcr-Abl tyrosine kinase of Philadelphia chromosome (Ph(1))-positive human leukemias. Ba p-1 is a substrate for the Bcr serine-threonine kinase and is also pho sphorylated on tyrosine by Bcr-Abl but not by c-Abl. Bap-1 may functio n in the regulation of c-Bcr and may contribute to the transforming ac tivity of Bcr-Abl in vivo. 14-3-3 proteins are essential for cell prol iferation and have a role in determining the timing of mitosis in yeas t. Through direct binding to sequences present in Bcr and in other pro teins implicated in signaling, the mammalian 14-3-3 proteins may link specific signaling protein components to mitogenic and cell-cycle cont rol pathways.