Figure: Regulation of Hippo signaling by MAP4K4 (Human).¶
The diagram illustrates the regulation of Hippo signaling by MAP4K4 in human cells, highlighting the key components of this pathway.
MAP4K4 (O95819) in the cytoplasm acts as a negative regulator of the Hippo pathway by inhibiting LATS1 (O95835) and LATS2 (Q9NRM7) kinases. This inhibition prevents the phosphorylation of the downstream effectors YAP1 (P46937) and WWTR1/TAZ (Q9GZV5).
In parallel, multiple regulatory interactions occur: the adaptor protein WWC1 (Q8IX03) activates STK3 (Q13188) and STK4 (Q13043), while SAV1 (Q9H4B6) serves as a kinase activator for these proteins. Additionally, MOB1A (Q9H8S9) and MOB1B (Q7L9L4) activate LATS1/2.
When LATS1/2 are active, they phosphorylate YAP1 and WWTR1, causing their cytoplasmic retention. However, when MAP4K4 inhibits LATS1/2, unphosphorylated YAP1 and WWTR1 can translocate to the nucleus where they interact with TEAD transcription factors (not explicitly shown in the original GO-CAM) to regulate gene transcription.
The diagram uses color-coding for different protein types (kinases, adaptors, coregulators) and directional arrows to indicate activation, inhibition, and translocation events within the Hippo signaling cascade.
Feedback from AI on figure:
{"feedback":"The diagram effectively captures the regulatory network of the Hippo signaling pathway with MAP4K4 as a central regulator. The spatial organization clearly distinguishes between cytoplasmic and nuclear events, and the addition of functional descriptions (e.g., kinase activator, Ser/Thr kinase) for each protein enhances understanding of their roles. The color-coding system and comprehensive legend make the diagram accessible to readers with varying levels of familiarity with signaling pathways.\n\nThe depiction of phosphorylation states for YAP1 and WWTR1 adds important regulatory context, illustrating how their localization changes based on phosphorylation status. The addition of the gene transcription indication in the nucleus effectively completes the signaling cascade, showing the ultimate outcome of pathway regulation.\n\nThe diagram maintains scientific accuracy while presenting the information in a visually appealing format suitable for publication in high-impact journals like Cell or Nature.","necessary_changes":null,"optional_changes":null}