SMAD3 and colonic neoplasm: Recently, the studies by Sekimoto et al and Matsuzaki et al have shown that TGF-β type I receptor (TβRI) phosphorylates Smad3 at the COOH-terminal (pSmad3C) thus inhibiting cell proliferation by up-regulating p21WAF1 in human gastric mucosa epithelial cells (RGM1) and human intestinal epithelial cells; the activated c-Jun N-terminal kinase (JNK) phosphorylates Smad3 at the Linker-terminal Ser-213 site (pSmad3L) to promote cell proliferation and carcinogenesis by up-regulating c-Myc in Ras-transformed human RGM1 cells and colon cancer cells [24, 25].