The Serine/theronine Kinase LKB1 Controls TCR Signalling and Positive Selection

The serine/theronine kinase LKB1 originally identified as a tumour suppressor regulates cell polarity, growth and development in many different cell types. However, with a high expression level in thymocytes, the role of LKB1 in T lineage cell development is largely unknown. Recently, a team led by Dr. LIU Xiaolong, at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS, provide novel insights of the role LKB1 played in thymocyte development. T-cell-specific deletion of LKB1 led to impaired normal thymocyte positive selection and generation of mature single positive thymocytes.

 

Positive selection initiated by TCR signal triggered by appropriate engagement of TCR and peptide-MHC complex is a process which drives the development of immature double positive thymocytes into mature single positive cells. After TCR engagement, loss of LKB1 led to attenuated activation of PLCγ1, one of the critical components of TCR signal transduction which induces the Ca²⁺ flux. In addition, LKB1 was directly phosphorylated by kinase Lck at tyrosine residues 36,261,365 and probably acted as a scaffold protein to enhance the recruitment of PLCγ1 to LAT signalosome following TCR stimulation. These observations indicated that LKB1 is required for thymocyte positive selection via regulation of TCR signal transduction.

 

This work entitled “LKB1 regulates TCR-mediated PLCγ1 activation and thymocyte positive selection” was on-line published in EMBO Journal on Apr 12^th, 2011.

 

This study was supported by the grants from the Ministry of Science and Technology, National Natural Science Foundation of China and Shanghai Municipal Commission for Science and Technology. (SIBCB)

 

AUTHOR CONTACT:

LIU Xiaolong

Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

Shanghai, China

Phone:86-21-54921176; Fax:86-21-54921178;E-mail: liux@sibs.ac.cn