Based on these findings, it is conceivable that as a central signal transducer, the tumor suppressor activities of Smad4 can be antagonized by oncogenic kinases through tyrosine phoshphoryaltion, thus serving as a major mechanism that favors tumorigenesis (Fig. 7h).36 Since a high proportion of tyrosine kinases account for more than half of the proto-oncogenes, whether more kinases can phosphorylate Smad4 or other Smad family members in cancer is also worth further exploration. The gene discussed is SMAD4; the disease is cancer.