Bcr encodes a GTPase-activating protein for p21rac

Abstract

MORE than thirty small guanine nucleotide-binding proteins related to the ras-encoded oncoprotein, termed Ras or p21^ras, are known¹. They regulate many fundamental processes in all eukaryotic cells, such as growth, vesicle traffic and cytoskeletal organization. GTPase-activating proteins (GAPs) accelerate the intrinsic rate of GTP hydrolysis of Ras-related proteins, leading to down-regulation of the active GTP-bound form². For p21^ras two GAP proteins are known, rasGAP and the neurofibromatosis (NF1) gene product^2–5. There is evidence that rasGAP may also be a target protein for regulation by Ras and be involved in downstream signalling^6–8. We have purified a GAP protein for p21^rho, which is involved in the regulation of the actin cytoskeleton⁹. Partial sequencing of rhoGAP reveals significant homology with the product of the bcr(breakpoint cluster region) gene, the translocation breakpoint in Philadelphia chromosome-positive chronic myeloid leukaemias. We show here that the carboxy-terminal domains of the bcr-encoded protein (Bcr) and of a Bcr-related protein, n-chimaerin, are both GAP proteins for the Ras-related GTP-binding protein, p21^rac. This result suggests that Bcr could be a target for regulation by Rac and has important new implications for the role of bcr translocations in leukaemia.