Figure 1.

SHP2 is a molecular switch of ESC self-renewal and/or differentiation. LIF-JAK-STAT3 signaling manipulates the ESC self-renewal, upregulation of SHP2 facilitates the ERK signals and inhibits LIF-JAK-STAT3 signal, while inhibition of SHP2 maintains the capacity of ESC self-renewal. Upon ESC differentiation, SHP2 acts a downstream effector of RTKs and triggers distinct major signal cascades and eventually regulates target gene expression. For example, SHP2 activates ERK and promotes ESC differentiation toward ectoderm and/or endoderm lineage differentiation.