title: Central role of paxillin phosphorylation in regulation of LFA-1 integrins activity and lymphocyte migration.
abstract: Coordinated changes of actin cytoskeleton and cell adhesion accompany maturation of lymphoid cells, their migration through lymphoid organs and to sites of inflammation, as well as metastasis of transformed cells. Here we discuss the central role of the actin-regulating adaptor protein, paxillin, during lymphocyte transition from a polarized, motile cell phenotype with partially active LFA-1 integrins to a round and immobile one with fully active LFA-1. In Baf3 murine pro-B lymphocytes, the former phenotype is induced by IL-3 that stimulates a FAK-mediated phosphorylation of paxillin at tyrosines (Y) 31 and 118 and a consequent Rac1 activation. Rearrangements of actin cytoskeleton that lead to the cell's acquisition of a spherical shape and LFA-1 activation are achieved upon activation of PKC-δ that binds and directly phosphorylates paxillin at threonine (T) 538 with consequent RhoA activation. This is accompanied by dephosphorylation of paxillin Y31/118 and by Rac1 inactivation. We propose a model of signaling cascades that reflects the interplay between the IL-3- and PKC-δ-mediated pathways.
authors.affiliation: Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA. romanovl@mail.nih.gov
authors.forename: Larisa Y
authors.initials: LY
authors.lastname: Romanova
authors.forename: J Frederic
authors.initials: JF
authors.lastname: Mushinski
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D051419:Paxillin / Q000378:metabolism*; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000378:metabolism; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D051419:Paxillin; D051745:Protein Kinase C-delta