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.

Lck 是一种 Src 相关蛋白酪氨酸激酶，与 CD4 和 CD8 分子结合，对 T 细胞发育和 T 细胞活化至关重要。Lck 的调节机制多种多样，关于每种机制的重要性存在争议。抑制性和激活性 Tyr 残基的磷酸化平衡由 CD45 和 Csk 之间的平衡维持，并依赖于完整的细胞内运输机制。目前的证据表明，脂质结合变化取决于 Lck 构象，并且 Lck 中磷酸化诱导的构象变化可能通过调节质膜上的 Lck 聚集来调节其激酶活性。ZAP-70 等下游调节器调节依赖于 Tyr ^{192 的}负反馈磷酸化。本综述详细研究了 Lck 的多种调节，强调了每种机制在维持每种构象状态中适量 Lck 方面的作用，从而允许在 TCR 刺激后有效、适当和受控地激活 T 细胞。