Bcr encodes a GTPase-activating protein for p21rac

Area of Science:

• Molecular biology
• Cell signaling
• Oncology

Background:

• Ras-related small GTPases are crucial regulators of eukaryotic cell functions.
• GTPase-activating proteins (GAPs) down-regulate GTP-bound Ras proteins by accelerating GTP hydrolysis.
• Known GAPs for p21ras include rasGAP and the neurofibromatosis (NF1) gene product.

Purpose of the Study:

• To identify and characterize novel GAPs for Ras-related proteins.
• To investigate the GAP activity of the breakpoint cluster region (Bcr) protein and related proteins.
• To explore the implications of Bcr's GAP activity in leukemia.

Main Methods:

• Purification of a GAP protein for p21rho.
• Partial sequencing of rhoGAP to identify homologies.
• Characterization of the carboxy-terminal domains of Bcr and n-chimaerin as GAPs for p21rac.

Main Results:

• A GAP protein for p21rho was purified, showing homology to the Bcr gene product.
• The carboxy-terminal domains of Bcr and n-chimaerin function as GAPs for the Ras-related GTP-binding protein, p21rac.
• This identifies Bcr as a potential target for regulation by Rac.

Conclusions:

• Bcr and n-chimaerin possess GAP activity towards p21rac.
• Bcr may be regulated by Rac, offering new insights into the role of bcr translocations in leukemia pathogenesis.