Feb 13, 2004 · Additional Shp2 functions downstream of, or parallel to, Ras/Erk activation also are proposed. Here, we show that Shp2 promotes Src family kinase (SFK) activation by regulating the phosphorylation of the Csk regulator PAG/Cbp, thereby controlling Csk access to SFKs.

In each tumor that was sensitive to combined treatment, p (Y542) SHP2 induction was observed in response to ERK signaling inhibition. The strategy was broadly effective in TNBC models and tumors with RAS mutations at G12, whereas tumors …

Oct 25, 2019 · To explain how the phosphatase activity of SHP-2 stimulates the RAS-ERK pathway, five mechanisms have been proposed. First, SHP-2 was shown to dephosphorylate specific positions of the receptor (e.g., PDGFR) or GAB thus preventing the recruitment of the RAS-GTPase activating protein RAS-GAP (Figure 2A) (47–51). Opposite to SOS, RAS-GAP ...

In this report, we describe several novel observations important for understanding the function of Shp-2 in promoting the Erk pathway. First, biochemical evidence suggests that Shp-2 acts upstream of Ras in the induction of Erk activity by EGF.

Feb 13, 2004 · Shp2 is required to sustain Ras/Erk activation in response to RTK stimulation. Recent studies implicate EM Ras activation, mediated via Src/Plcγ1-dependent stimulation of RasGRPs, in this process (Bivona et al., 2003).

Nov 15, 2022 · These analyses revealed altered levels of phosphorylation in persistent cells, including peptides belonging to SHP2, an oncogenic phosphatase known to regulate JAK-STAT signaling as well as RAS-ERK activation and which has been shown to contribute to adaptive resistance to targeted cancer therapies.

Jan 2, 2019 · In each tumor that was sensitive to combined treatment, p(Y542)SHP2 induction was observed in response to ERK signaling inhibition. The strategy was broadly effective in TNBC models and tumors with RAS mutations at G12, whereas tumors with RAS(G13D) or RAS(Q61X) mutations were resistant.

Sep 6, 2022 · The rat sarcoma (Ras)/ERK pathway is a well-established major signaling pathway modulated by SHP2 downstream of RTKs in different cell types [1, 10, 123]. SHP2 regulates cell proliferation, survival, differentiation, migration and metabolism primarily through activation of this pathway [28, 122].

Encoded by PTPN11, the SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase-2) is widely recognized as a carcinogenic phosphatase. As a promising anti-cancer drug target, SHP2 regulates many signaling pathways such …

Mar 5, 2019 · Here, we found that expressing the NS-associated mutant SHP2 D61G in excitatory, but not inhibitory, hippocampal neurons increased ERK signaling and impaired both long-term potentiation (LTP) and spatial memory in mice, although endogenous SHP2 was expressed in both neuronal types.