Figure 5.

SMAD linker modifications alter Transforming growth factor β (TGFβ) signaling. The SMAD proteins consist of a MH1 and MH2 domain, connected with a non-conserved linker domain. Threonine and serine residues in the linker domain can be modulated by protein kinases and phosphatases like mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinases (JNK), and Glycogen synthase kinase 3 (GSK-3). These kinases can be activated by growth factors and inflammatory mediators. This process greatly affects SMAD function and leads to altered TGFβ signaling.