ArticleMolecular and cellular biology1996
Mutational analysis of Lck in CD45-negative T cells: dominant role of tyrosine 394 phosphorylation in kinase activity.
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity.Immunology · 2012Pooled it
- Loss of ST8Sia6 mediated α-2,8-linked di-sialylation enhances T cell-dependent antibody responses and promotes autoimmunity in aged mice.Frontiers in immunology · 2026Article
- Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1.Nature reviews. Immunology · 2023Review
- The role of competing mechanisms on Lck regulation.Immunologic research · 2020Review
- Conformational States Control Lck Switching between Free and Confined Diffusion Modes in T Cells.Biophysical journal · 2020Article
- Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Biophysical basis underlying dynamic Lck activation visualized by ZapLck FRET biosensor.Science advances · 2019Article
- Overexpression of Csk-binding protein/phosphoprotein associated with glycosphingolipid-enriched microdomains induces cluster of differentiation 59-mediated apoptosis in Jurkat cells.Experimental and therapeutic medicine · 2018Article
- Review
- Encoding optical control in LCK kinase to quantitatively investigate its activity in live cells.Nature structural & molecular biology · 2017Article
- The human cytomegalovirus glycoprotein pUL11 acts via CD45 to induce T cell IL-10 secretion.PLoS pathogens · 2017Article
- Review
- In vitro membrane reconstitution of the T-cell receptor proximal signaling network.Nature structural & molecular biology · 2014Article
- The RNA-binding protein hnRNPLL induces a T cell alternative splicing program delineated by differential intron retention in polyadenylated RNA.Genome biology · 2014Article
- Article
- Focal adhesion kinase negatively regulates Lck function downstream of the T cell antigen receptor.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Subcellular distribution of Lck during CD4 T-cell maturation in the thymic medulla regulates the T-cell activation threshold.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis of T cells.PLoS pathogens · 2011Article
- Article
- Lyn kinase and ZAP70 are substrates of PTPROt in B-cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF-R inhibitor pazopanib.Journal of cellular biochemistry · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CD45 tyrosine phosphatase has been reported to activate the src family tyrosine kinases Lck and Fyn by dephosphorylating regulatory COOH-terminal tyrosine residues 505 and 528, respectively. However, recent studies with CD45- T-cell lines have found that despite the fact that Lck and Fyn were constitutively hyperphosphorylated, the tyrosine kinase activity of both enzymes was actually increased. In the present study, phosphoamino acid analysis revealed that the increased phosphorylation of Lck in CD45- YAC-1 T cells was restricted to tyrosine residues. To understand the relationship between tyrosine phosphorylation and Lck kinase activity, CD45- YAC-1 cells were transfected with forms of Lck in which tyrosines whose phosphorylation is thought to regulate enzyme activity (Tyr-192, Tyr-394, Tyr-505, or both Tyr-394 and Tyr-505) were replaced with phenylalanine. While the Y-to-F mutation at position 192 (192-Y-->F) had little effect, the 505-Y-->F mutation increased enzymatic activity. In contrast, the 394-Y-->F mutation decreased the kinase activity to very low levels, an effect that the double mutation, 394-Y-->F and 505Y-->F, could not reverse. Phosphopeptide analysis of tryptic digests of Lck from CD45- YAC-1 cells revealed that it is hyperphosphorylated on two tyrosine residues, Tyr-505 and, to a lesser extent, Tyr-394. The purified and enzymatically active intracellular portion of CD45 dephosphorylated Lck Tyr-394 in vitro. These results demonstrate that in addition to Tyr-505, CD45 can dephosphorylate Tyr-394, and that in the absence of CD45 the hyperphosphorylation of Tyr-394 can cause an increase in the kinase activity of Lck despite the inhibitory hyperphosphorylation of Tyr-505. Therefore, Lck kinase activity is determined by the balance of activating and inhibitory tyrosine phosphorylations that are, in turn, regulated by CD45.
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