The adaptor protein 3BP2 in leukocyte signaling

Adaptor proteins that do not contain intrinsic enzymatic activity play a critical role in cell biology by regulating the assembly of large multimolecular signaling complexes involved in extracellular signal transduction. The increasing number of diseases associated with aberrant function or expression of adaptor proteins further illustrate their key role in cellular regulation. The adaptor 3BP2 (or SH3BP2) was originally identified more than 10 years ago as an c-Abl binding protein, and next as a partner of Syk family kinases in 1998. 3BP2 displays the typical modular organization of an adapter protein with an amino-terminal PH domain, a central proline rich region and a carboxyl-terminal SH2 domain. Although its physiological function remains unknown, studies have implicated a role for 3BP2 in immunoreceptor signaling through its interaction with a number of signaling molecules including Src and Syk families of protein tyrosine kinases, the membrane adaptor LAT, Vav exchange factors, PLC-gamma, and 14-3-3 proteins. Recently, the 3bp2/sh3bp2 locus was shown to be mutated in a rare human disease involved in cranial-facial development called cherubism, suggesting a role for 3BP2 in regulating osteoclast and hematopoietic cell function.