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The role of competing mechanisms on Lck regulation

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Abstract

Lck is a Src-related protein tyrosine kinase that associates with CD4 and CD8 molecules and is essential to T cell development and T cell activation. Regulatory mechanisms of Lck are diverse and controversy exists regarding the importance of each mechanism. The balance of phosphorylation at the inhibitory and activating Tyr residues is maintained by a balance between CD45 and Csk and is dependent upon intact intracellular trafficking machinery. Current evidence shows that lipid-binding changes depending on Lck conformation and that phosphorylation-induced conformational changes in Lck modulate its kinase activity potentially through regulation of Lck clustering at the plasma membrane. Downstream regulators such as ZAP-70 mediate negative feedback that is dependent on Tyr192 phosphorylation. This review examines the diverse regulation of Lck in detail, highlighting the role of each mechanism on maintaining an appropriate amount of Lck in each conformational state, thus allowing for an efficient, appropriate, and controlled amount of T cell activation following TCR stimulation.

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Authors and Affiliations

  1. Division of Cardiac Surgery, Department of Surgery, University of Alberta, Edmonton, Canada

    Sabin J. Bozso & Jeevan Nagendran

  2. Li Ka Shing Health Research Centre, University of Alberta, 4-050, Edmonton, AB, Canada

    Sabin J. Bozso & Jeevan Nagendran

  3. Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

    Jimmy J. H. Kang

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Bozso, S.J., Kang, J.J.H. & Nagendran, J. The role of competing mechanisms on Lck regulation. Immunol Res 68, 289–295 (2020). https://doi.org/10.1007/s12026-020-09148-2

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