Activation and Function of the Rap1 Gtpase in B Lymphocytes

Rap1 is a monomeric GTPase that is closely related to Ras. In this review, we summarize our recent work showing that the B cell antigen receptor (BCR), as well as chemokine receptors, activate Rap1 via a pathway that involves phospholipase C-dependent production of diacylglycerol (DAG). The possible identities of the DAG-regulated guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that regulate the activation of Rap1 by the BCR and chemokine receptors will be discussed. Although initially thought to be an antagonist of Ras-mediated signaling, Rap1 does not appear to modulate the ability of the BCR to activate downstream targets of Ras. Instead, activation of Rap1 promotes B cell adhesion as well as B cell migration toward chemokines. Thus, Rap1 may play a key role in a number of processes that are essential for B cell development and activation.