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. 2023 Feb 23;220(5):e20221563. doi: 10.1084/jem.20221563

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© 2023 Wei et al.

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Figure 7. — Model showing sites of action of INPPL1, MAP4K5, and LZTR1. SHP2 plays a positive role for RAS activation upstream of SOS. INPPL1 works both upstream and downstream of RAS, negatively regulating ERK activity. However, INPPL1 deletion confers SHP099 resistance mainly by its actions downstream of RAS. MAP4K5 acts downstream of RAS, but upstream of MEK. LZTR1 can act on RAS proteins or RIT1 but confers SHP099 resistance mainly through the latter.