Dephosphorylation of Lck-pY505 by CD45

Stable Identifier
Reaction [transition]
Homo sapiens
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TCR stimulation induce the transient dephosphorylation of PAG thereby release the Csk from its plasma membrane anchor. The release of Csk from its proximity with Lck may serve to facilitate the activation of Lck.Protein tyrosine phosphtase CD45 (PTPRC) and CD148 (PTPRJ) have dual function in TCR signalling. They act both in activation as well as inactivation of Src family kinases (SFKs) which are involved in the initiation of TCR signal transduction (Stepanek et al. 2011). The activatory role is to dephosphorylate an inhibitory site tyrosine 505 (Y505) at the C-terminal end of Lck, which is needed to enable Lck to an open conformation and expose the activation loop (A-loop) containing the activating tyrosine 394 (Y394) (Xu et al. 1993. McNeill et al. 2007, Zikherman et al. 2010, Stepanek et al. 2011, Salmond et al. 2009).
Literature References
PubMed ID Title Journal Year
20346773 CD45-Csk phosphatase-kinase titration uncouples basal and inducible T cell receptor signaling during thymic development

Watson, S, Weiss, A, Goodnow, CC, Zikherman, J, Raschke, W, Jenne, C, Doan, K

Immunity 2010
21543337 Regulation of Src family kinases involved in T cell receptor signaling by protein-tyrosine phosphatase CD148

Draber, P, Stepanek, O, Brdicka, T, Weiss, A, Angelisová, P, Horejsí, V, Svojgr, K, Kalina, T, Skopcova, T

J. Biol. Chem. 2011
11827988 Adapters in lymphocyte signaling

Horejsi, V, Wienands, J, Leo, A, Baier, G, Schraven, B

J Clin Invest 2002
2530588 Expression of CD45 alters phosphorylation of the lck-encoded tyrosine protein kinase in murine lymphoma T-cell lines

Hurley, TR, Sefton, BM, Trowbridge, IS, Johnson, P, Ostergaard, HL, Hyman, R, Shackelford, DA

Proc. Natl. Acad. Sci. U.S.A. 1989
23580664 The large ectodomains of CD45 and CD148 regulate their segregation from and inhibition of ligated T-cell receptor

Bridge, M, van der Merwe, PA, Choudhuri, K, Basat, AB, Cordoba, SP, Zhang, H, Dustin, ML

Blood 2013
Catalyst Activity

protein tyrosine phosphatase activity of CD45,CD148 [plasma membrane]

Orthologous Events
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