Reactome | Dephosphorylation of Lck-pY505 by CD45

Dephosphorylation of Lck-pY505 by CD45

Stable Identifier

R-HSA-202214

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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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 Zikherman, J, Jenne, C, Watson, S, Doan, K, Raschke, W, Goodnow, CC, Weiss, A	Immunity	2010
21543337	Regulation of Src family kinases involved in T cell receptor signaling by protein-tyrosine phosphatase CD148 Stepanek, O, Kalina, T, Draber, P, Skopcova, T, Svojgr, K, Angelisová, P, Horejsí, V, Weiss, A, Brdicka, T	J. Biol. Chem.	2011
11827988	Adapters in lymphocyte signaling Leo, A, Wienands, J, Baier, G, Horejsi, V, 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 Ostergaard, HL, Shackelford, DA, Hurley, TR, Johnson, P, Hyman, R, Sefton, BM, Trowbridge, IS	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 Cordoba, SP, Choudhuri, K, Zhang, H, Bridge, M, Basat, AB, Dustin, ML, van der Merwe, PA	Blood	2013