Shaping immune responses through the activation of dendritic cells–P2 receptors

Dendritic cells (DCs) activate and shape the adaptive immune response by capturing antigens, migrating to peripheral lymphoid organs where naïve T cells reside, expressing high levels of MHC and costimulatory molecules and secreting cytokines and chemokines. DCs are endowed with a high degree of functional plasticity and their functions are tightly regulated. Besides initiating adaptive immune responses, DCs play a key role in maintaining peripheral tolerance toward self-antigens. On the basis of the information gathered from the tissue where they reside, DCs adjust their functional activity to ensure that protective immunity is favoured while unwanted or exaggerated immune responses are prevented. A wide variety of signals from neighbouring cells affecting DC functional activity have been described. Here we will discuss the complex role of extracellular nucleotides in the regulation of DC function and the role of P2 receptors as possible tools to manipulate immune responses

N-terminal Dbl domain of the RhoGEF, Kalirin.

Guanine nucleotide exchange factors (GEF) promote the release of GDP from GTPases, thus allowing the free GTPase molecule to bind the more abundant GTP molecule. In the GTP-bound state, the GTPase elicits signal transduction by acting on its effector proteins. Spontaneous release of GDP is a slow process and the catalysis of the GDP release by a GEF is generally a prerequisite for efficient signaling (Vetter and Wittinghofer 2001). The structurally related GEFs form subfamilies that regulate a specific family of GTPase proteins. GEFs that activate Rho GTPases have been implicated in cancer and mental retardation. RhoGEFs are a relatively large family, and many of the *69 human RhoGEFs were discovered based on their oncogenic activation in cancer and cancer models. The catalytic components of RhoGEFs are referred to as Dbl homology domains, after the screen that identified the protein Dbl encoded by the diffuse B-cell lymphoma (dbl) oncogene (Eva and Aaronson 1985). Thus the RhoGEF family is a potential target for treating tumors and cancer