Editors' ChoiceImmunology

LAT-free Signaling

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Science's STKE  06 Feb 2001:
Vol. 2001, Issue 68, pp. tw4
DOI: 10.1126/stke.2001.68.tw4

T cell receptor (TCR) signaling involves the activation of multiple pathways leading to such outputs as changes in gene expression and cytoskeletal rearrangements. Ku et al. used genetically engineered T cell lines and transfection experiments to investigate the mechanism by which activated TCRs can stimulate the kinase PAK1. PAK1 activation did not require the transmembrane adaptor LAT or the cytosolic adaptors SLP-76 and Nck, but did require the Src-like kinase ZAP-70. Instead PAK1 activation depended on PAK-interacting protein (PIX), which is a guanine exchange factor for Rho guanosine triphosphatases (GTPases), and also depended on a PIX-interacting protein PKL. Although PAK1 kinase activity required the binding of a GTPase, that GTPase was not Ras or Rac1, because activation of both of these GTPases depended on LAT. Thus, the authors propose that there are two separate pathways from the TCR that diverge at the level of ZAP-70: one proceeds through LAT and the other proceeds through the PAK1-PIX-PKL complex.

G. M. Ku, D. Yablonski, E. Manser, L. Lim, A. Weiss, A PAK-1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT. EMBO J. 20, 457-465 (2001). [Abstract] [Full Text]