Reactome: A Curated Pathway Database

SHP1 and SHP2 bind the common beta chain

Stable Identifier
Homo sapiens
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The common beta chain (Bc) has at least at least one direct binding site for SHP-1/SHP-2 (PTPN6/PTPN11). The SH2 domains of SHP1 and SHP2 associate with Y628 of Bc following IL-3 stimulation (Pei et al. 1994, Bone et al. 1997). SHPs act as regulators of signaling. SHP1 is thought to be a negative regulator of growth that terminates signals. Binding of SHP1 to EpoR leads to SHP1 activation and dephosphorylation of JAK2, terminating proliferative signals (Klingmuller et al. 1995). SHP1 has also been shown to interact directly and dephosphorylate JAK2 (Jiao et al. 1996). Although SHP-2 competes for the same binding site, it is thought to be a positive modulator. SHP2 associates with JAK1/2 and is phosphorylated at Y304 by these kinases, creating a GRB2 recognition motif (Yin et al. 1997). IL-3 induces the phosphorylation of SHP2 and its association with Grb2 (Welham et al. 1994). SHP2 could thereby act as an adaptor between Bc and Grb2 leading to activation of the ras/mitogen-activated protein kinase pathway. SHP2 can also associate with the p85 subunit of phosphatidylinositol 3-kinase (Welham et al. 1994) so SHP2 may also regulate this pathway.

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Orthologous Events