Meta-Biol

• Pathways

PTPN11 (SHP2) is tyrosine-phosphorylated in a JAK1-dependent manner (Schaper et al. 1998, Lehmann et al. 2003, Fischer, 2004). Cells lacking JAK1 showed drastically reduced PTPN11 phosphorylation following Interleuikin-6 (IL6) treatment, but it is not entirely clear whether JAK1 directly phosphorylates PTPN11 or alternatively is required for IL6ST activation, which indirectly leads to PTPN11 phosphorylation (Schaper et al, 1998). PTPN11 tyrosine phosphorylation at Y546 or Y584 (usually described as Y542 or Y580 in literature references where numbering is based on a short isoform) relieves the PTP domain from the N-SH2 domain-mediated inhibition (Lu et al. 2001). Studies using catalytically-inactive PTPN11 (Symes et al. 1997) suggest that it may dephosphorylate IL6ST and/or associated signaling factors such as JAKs and STATs, limiting acute phase gene expression (Kim and Baumann, 1999). There is a consensus that SHP2 is involved in IL6-induced activation of the MAPK pathway, but the molecular details are unclear.