RT Journal Article
T1 An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
A1 Antón Hurtado, Olga María
A1 Batista, Alicia
A1 Millán, Jaime
A1 Andrés-Delgado, Laura
A1 Puertollano, Rosa
A1 Correas, Isabel
A1 Alonso, Miguel A.
AB The MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. The src family kinase Lck plays a pivotal role in T cell signaling. We show that MAL is required in T cells for efficient expression of Lck at the plasma membrane and activation of IL-2 transcription. To investigate the mechanism by which MAL regulates Lck targeting, we analyzed the dynamics of Lck and found that it travels to the plasma membrane in specific transport carriers containing MAL. Coimmunoprecipitation experiments indicated an association of MAL with Lck. Both carrier formation and partitioning of Lck into detergent-insoluble membranes were ablated in the absence of MAL. Polarization of T cell receptor for antigen (TCR) and microtubule-organizing center to immunological synapse (IS) were also defective. Although partial correction of the latter defects was possible by forced expression of Lck at the plasma membrane, their complete correction, formation of transport vesicles, partitioning of Lck, and restoration of signaling pathways, which are required for IL-2 transcription up-regulation, were achieved by exogenous expression of MAL. We concluded that MAL is required for recruitment of Lck to specialized membranes and formation of specific transport carriers for Lck targeting. This novel transport pathway is crucial for TCR-mediated signaling and IS assembly.
PB Rockefeller University Press
SN 1540-9538
YR 2008
FD 2008
LK https://hdl.handle.net/20.500.14352/96980
UL https://hdl.handle.net/20.500.14352/96980
LA eng
NO Olga Antón, Alicia Batista, Jaime Millán, Laura Andrés-Delgado, Rosa Puertollano, Isabel Correas, Miguel A. Alonso; An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes . J Exp Med 22 December 2008; 205 (13): 3201–3213. doi: https://doi.org/10.1084/jem.20080552
NO Ministerio de Educación y Ciencia (España)
NO National Institute of Health (USA)
DS Docta Complutense
RD 6 abr 2025