Samantha Rickard^1,2, Qian Wang^2,3, Christopher Squire^2,4, Julie Spicer^2,5, Peter Shepherd^2,3,5, Jack Flanagan^1,2,5.

¹Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand. ²Maurice Wilkins Centre, Auckland, New Zealand. ³Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand. ⁴School of Biological Sciences, The University of Auckland, Auckland, New Zealand. ⁵Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.

T-cell activity contributes to the pathophysiology of organ transplant rejection, multiple autoimmune diseases and the side effects of cancer immunotherapies. Lymphocyte specific kinase (Lck) is an essential component of signalling in T-cells and acts immediately downstream of the T-cell receptor (TCR). Loss-of-function mutations of Lck in humans result in severe defects in the immune response and pointed to this enzyme as a drug target in T-cell driven autoimmune disease. Auto-transphosphorylation of tyrosine 394 (Y394) on the activation loop of Lck is required for activity. This phosphorylation is sensitive to ATP site