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Fig. 1. Non-Smad signalling. The canonical Smad pathway starting from the ligand-receptor complex and ending in the nucleus is illustrated by thick black arrows. Non-Smad signalling mechanisms are shown by thin blue arrows. The receptor complex activates (by interaction and/or phosphorylation) protein X, which then modulates the activity of the Smad (pathway 1). The phosphorylated Smad activates (by interaction) protein Y, which then transmits further signals into the cell (pathway 2). The receptor complex activates (by interaction and/or phosphorylation) protein Z, which then transmits signals without direct crosstalk with the Smad (pathway 3). Proteins X, Y and Z can be enzymes (e.g. protein or lipid kinases) or adaptor proteins.





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