Figure 6.

Loss of RSK2-mediated feedback pathway helps promote proliferation and survival of SHP2-deficient BMMs. A) Mutation of Ser711 on M-CSFR leads to increased phosphorylation on M-CSFR Tyr721 and enhanced M-CSF–evoked AKT activation. RAW264.7 cells expressing the indicated EPOR/M-CSFR chimera were starved (−) and then stimulated with 5 U/ml EPO for the indicated times (+). Cell lysates were immunoprecipitated with anti-FLAG antibody and then immunoblotted with the indicated antibodies. Note that the Ser711-Ala mutant shows decreased reactivity with anti-pPKA antibodies and increased reactivity with anti-pTyr and -pTyr721 antibodies. Data shown are representative of the 3 independent experiments. B) Model for RSK-mediated, negative-feedback pathway in comparison with p70S6 kinase-mediated feedback signaling loop. See text for details.