Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2002 Jan;109(1):9-14.
doi: 10.1172/JCI14794.

Reciprocal regulation of lymphocyte activation by tyrosine kinases and phosphatases

Michelle L Hermiston  1 , Zheng Xu, Ravindra Majeti, Arthur Weiss
Affiliations
Review

Reciprocal regulation of lymphocyte activation by tyrosine kinases and phosphatases

Michelle L Hermiston et al. J Clin Invest. 2002 Jan.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Speculative model for reciprocal regulation of tyrosine phosphorylation in lymphocytes. We hypothesize that Lck traffics between rafts and other subcellular pools based upon its tyrosine phosphorylation status. (a) Thus, in the resting T cell, Lck is in a dynamic equilibrium between its inactive and primed conformations due to the reciprocal activity of the phosphatase CD45RA+ and the kinase Csk/PEP. (b) Upon T cell activation, rafts coalesce and an immunological synapse forms. CD45RA+ is excluded from the immunological synapse due to its size. PAG is dephosphorylated by an unknown phosphatase, resulting in release of Csk/PEP. Unopposed, primed Lck is thus able to undergo transphosphorylation at Y394, which yields an active kinase that subsequently phosphorylates the ITAMs of the CD3 and ζ chains. The phosphorylated ITAMs provide docking sites for the SH2 domains of ZAP-70. ZAP-70 is further phosphorylated by Lck, and activation of downstream signaling events ensues. (c) During downregulation, the CD45RO isoform is inactivated by homodimerization. PAG is again phosphorylated, recruiting Csk/PEP to the raft, where Lck becomes phosphorylated at Y505 and dephosphorylated at Y394, leaving this kinase in an inactive conformation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Li L, Dixon JE. Form, function, and regulation of protein tyrosine phosphatases and their involvement in human diseases. Semin Immunol. 2000; 12:75–84. - PubMed
    1. Kane LP, Lin J, Weiss A. Signal transduction by the TCR for antigen. Curr Opin Immunol. 2000; 12:242–249. - PubMed
    1. Billadeau, D.D., and Leibson, P.J. 2002. ITAMs versus ITIMs: striking a balance during cell regulation. J. Clin. Invest . In press. - PMC - PubMed
    1. Tomlinson MG, Lin J, Weiss A. Lymphocytes with a complex: adapter proteins in antigen receptor signaling. Immunol Today. 2000; 21:584–591. - PubMed
    1. Ferrell JE. How regulated protein translocation can produce switch-like responses. Trends Biochem Sci. 1998; 18:416–465. - PubMed

Publication types

MeSH terms

Substances