Anti-RAC1 / Cdc42 (N-terminal) polyclonal antibody

To explore the contribution of Vav1, a hematopoietic signal transducer, to pancreatic ductal adenocarcinoma (PDAC) development, we generated transgenic mouse lines expressing, Vav1, K-Ras(G12D), or both K-Ras(G12D) and Vav1 in pancreatic acinar cells. Co-expression of Vav1 and K-Ras(G12D) synergistically enhanced acinarto-ductal metaplasia (ADM) formation, far exceeding the number of lesions developed in K-Ras(G12D) mice. Mice expressing only Vav1 did not develop ADM. Moreover, the incidence of PDAC in K-Ras(G12D)/Vav1 was significantly higher than in K-Ras(G12D) mice. Discontinuing Vav1 expression in K-Ras(G12D)/Vav1 mice elicited a marked regression of malignant lesions in the pancreas, demonstrating Vav1 is required for generation and maintenance of ADM. Rac1-GTP levels in the K-Ras(G12D)/Vav1 mice pancreas clearly demonstrated an increase in Rac1 activity. Treatment of K-Ras(G12D) and K-Ras(G12D)/Vav1 mice with azathioprine, an immune-suppressor drug which inhibits Vav1's activity as a GDP/GTP exchange factor, dramatically reduced the number ofmalignant lesions. These results suggest that Vav1 plays a role in the development of PDAC when co-expressed with K-Ras(G12D) via its activity as a GEF for Rac1GTPase.

Spatially-organized spontaneous activity is a characteristic feature of developing mammalian sensory systems. However, the transitions of spontaneous-activity spatial organization during development and related mechanisms remain largely unknown. We reported previously that layer 4 (L4) glutamatergic neurons in the mouse barrel cortex exhibit spontaneous activity with a patchwork-type pattern at postnatal day (P)5, which is during barrel formation. In the current work, we revealed that spontaneous activity in mouse barrel-cortex L4 glutamatergic neurons exhibits at least three phases during the first two weeks of postnatal development. Phase I activity has a patchwork-type pattern and is observed not only at P5, but also P1, before barrel formation. Phase II is found at P9, by which time barrel formation is completed, and exhibits broadly synchronized activity across barrel borders. Phase III emerges around P11 when L4-neuron activity is desynchronized. The Phase I activity, but not Phase II or III activity, is blocked by thalamic inhibition, demonstrating that the Phase I to II transition is associated with loss of thalamic dependency. Dominant-negative (DN)-Rac1 expression in L4 neurons hampers the Phase II to III transition. It also suppresses developmental increases in spine density and excitatory synapses of L4 neurons in the second postnatal week, suggesting that Rac1-mediated synapse maturation could underlie the Phase II to HI transition. Our findings revealed the presence of distinct mechanisms for Phase I to II and Phase H to HI transition. They also highlighted the role of a small GTPase in the developmental desynchronization of cortical spontaneous activity.