BMP, PTEN and Wnt/beta-catenin pathways are the three signaling pathways that 
control normal development and regeneration of the intestine, and contribute to 
intestinal polyposis when aberrant inactivation or activation occurs in each of 
these pathways. Using genetic targeting of BMPR1A in mice, we show that 
inactivation of BMP signaling results in multiple polyps due to an increased 
number of crypts and stem cells, accompanied by enhanced Wnt signaling in all 
proliferating intestine cells. However the increased transcriptional activity of 
Wnt effecter protein, beta-catenin, is found primarily in intestine stem cells 
(ISCs). Concurrently, PTEN, an inhibitor of PI3K/Akt pathway, is also primarily 
inactivated in the ISCs, leading to activation of Akt. Thus, Akt may contribute 
to activation of beta-catenin in ISCs in coordination with Wnt signaling. By 
conducting a proteomic analysis of the beta-catenin complex, we show that 
14-3-3zeta exists in the beta-catenin complex and facilitates activation of 
beta-catenin by Akt, which, intriguingly, appears to be predominantly in ISCs. 
Thus, we propose that BMP signaling plays a role in inhibition of ISC 
self-renewal through suppression of Wnt/beta-catenin signaling in ISC, and this 
cross-talk is bridged, at least in part, through the PTEN/Akt pathway and 
further enforced by 14-3-3zeta.