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TGF-β/BMP and RTK/Ras-activated MAPK and PI3K/Akt pathways. The MAPK and PI3K/Akt pathways impinge on TGF-β/BMP signaling primarily by modulating Smad functions. MAPKs and Akt bind and/or phosphorylate R-Smads to control their intracellular distribution and transcriptional activity. MAPKs and Akt also phosphorylate and regulate a variety of Smad binding partners in the nucleus, indirectly affecting the Smads.
