SHC1 binds PTPN12

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

Phosphorylation of SHC1 splicing isoforms SHC1-1 (p66Shc) and SHC1-2 (p52Shc) on serine residues S139 and S29, respectively, by the activated protein kinase C enables SHC1 binding to protein tyrosine phosphatase PTPN12 (PTP-PEST) (Habib et al. 1994, Faisal et al. 2002). The interaction between SHC1 and PTPN12 involves the phosphotyrosine interaction domain (PID) of SHC1 and the NPLH motif of PTPN12. The NPLH motif of PTPN12 resembles the SHC1-binding NPXY motif of receptor tyrosine kinases. It is possible that phosphorylation of PTPN12 on histidine residue of the NPLH sequence, similar to phosphorylation of tyrosine residue in the NPXY motif, precedes SHC1 binding (Medzihradszky et al. 1997, Zheng et al. 2013). Once bound to SHC1, PTPN12 likely dephosphorylates tyrosine residues of SHC1, thus attenuating SHC1-mediated downstream signaling from activated receptor tyrosine kinases (Davidson and Veillette 2001, Faisal et al. 2002, Zheng et al. 2013).

Literature References
PubMed ID Title Journal Year
7929214 Activators of protein kinase C stimulate association of Shc and the PEST tyrosine phosphatase

Habib, T, Herrera, R, Decker, SJ

J. Biol. Chem. 1994
9232641 Synthesis and characterization of histidine-phosphorylated peptides

Medzihradszky, KF, Phillipps, NJ, Senderowicz, L, Wang, P, Turck, CW

Protein Sci. 1997
23846654 Temporal regulation of EGF signalling networks by the scaffold protein Shc1

Zheng, Y, Zhang, C, Croucher, DR, Soliman, MA, St-Denis, N, Pasculescu, A, Taylor, L, Tate, SA, Hardy, WR, Colwill, K, Dai, AY, Bagshaw, R, Dennis, JW, Gingras, AC, Daly, RJ, Pawson, T

Nature 2013
12052829 Serine/threonine phosphorylation of ShcA. Regulation of protein-tyrosine phosphatase-pest binding and involvement in insulin signaling

Faisal, A, El-Shemerly, M, Hess, D, Nagamine, Y

J. Biol. Chem. 2002
11432829 PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates

Davidson, D, Veillette, A

EMBO J. 2001
Participant Of
Orthologous Events