65-Kilodalton protein phosphorylated by interleukin 2 stimulation bears two putative actin-binding sites and two calcium-binding sites

Zu, Youli; Shigesada, Katsuya; Nishida, Eisuke; Kubota, Ichiro; Kohno, Michiaki; Hanaoka, Masao; Namba, Yoshiharu

doi:10.1021/bi00488a017

Cited by 28 publications

(16 citation statements)

References 34 publications

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“…Initial experiments revealed that L-plastin was phosphorylated at Ser 5 in IL-2-cultured human T lymphocytes (Supplemental Fig. 1A), which is consistent with reports that IL-2 induces L-plastin phosphorylation in T lymphocytes (24). Culturing the cells overnight in the absence of IL-2 or serum-starving the cells for 2 h in RPMI 1640 containing 0.5% BSA was sufficient to reduce the high basal levels of phosphorylation of L-plastin and ERK (Supplemental Fig.…”

Section: Resultssupporting

confidence: 90%

L-Plastin Regulates Polarization and Migration in Chemokine-Stimulated Human T Lymphocytes

Freeley

O’Dowd

Paul

et al. 2012

The Journal of Immunology

105

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Chemokines such as SDF-1α play a crucial role in orchestrating T lymphocyte polarity and migration via polymerization and reorganization of the F-actin cytoskeleton, but the role of actin-associated proteins in this process is not well characterized. In this study, we have investigated a role for L-plastin, a leukocyte-specific F-actin–bundling protein, in SDF-1α–stimulated human T lymphocyte polarization and migration. We found that L-plastin colocalized with F-actin at the leading edge of SDF-1α–stimulated T lymphocytes and was also phosphorylated at Ser5, a site that when phosphorylated regulates the ability of L-plastin to bundle F-actin. L-plastin phosphorylation was sensitive to pharmacological inhibitors of protein kinase C (PKC), and several PKC isoforms colocalized with L-plastin at the leading edge of SDF-1α–stimulated lymphocytes. However, PKC ζ, an established regulator of cell polarity, was the only isoform that regulated L-plastin phosphorylation. Knockdown of L-plastin expression with small interfering RNAs demonstrated that this protein regulated the localization of F-actin at the leading edge of chemokine-stimulated cells and was also required for polarization, lamellipodia formation, and chemotaxis. Knockdown of L-plastin expression also impaired the Rac1 activation cycle and Akt phosphorylation in response to SDF-1α stimulation. Furthermore, L-plastin also regulated SDF-1α–mediated lymphocyte migration on the integrin ligand ICAM-1 by influencing velocity and persistence, but in a manner that was independent of LFA-1 integrin activation or adhesion. This study, therefore, demonstrates an important role for L-plastin and the signaling pathways that regulate its phosphorylation in response to chemokines and adds L-plastin to a growing list of proteins implicated in T lymphocyte polarity and migration.

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Section: Resultssupporting

confidence: 90%

L-Plastin Regulates Polarization and Migration in Chemokine-Stimulated Human T Lymphocytes

Freeley

O’Dowd

Paul

et al. 2012

The Journal of Immunology

105

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“…The leukocyte (L)-plastin (LPL, also called plastin 2) isoform is exclusively expressed in mammalian leukocytes and is the only plastin isoform present in leukocytes. A serine site close to the N-terminus is phosphorylated by various immunological stimuli such as IL-2 or TCR ligands in T cells (24, 25). LPL has been shown to have a role in function of both neutrophils and T cells.…”

Section: Introductionmentioning

confidence: 99%

Actin-Bundling Protein L-Plastin Regulates T Cell Activation

Wang

Morley

Donermeyer

et al. 2010

The Journal of Immunology

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Engagement of TCRs induces actin rearrangements, which are critical for T cell activation. T cell responses require new actin polymerization, but the significance of higher-order actin structures, such as microfilament bundles, is unknown. To determine the role of the actin-bundling protein leukocyte-plastin (L-plastin; LPL) in this process, T cells from LPL−/− mice were studied. LPL−/− T cells were markedly defective in TCR-mediated cytokine production and proliferation. LPL−/− T cells also spread inefficiently on surfaces with immobilized TCR ligands and formed smaller immunological synapses with APCs, likely due to defective formation of lamellipodia. LPL−/− mice showed delayed rejection of skin allografts after release from immunosuppression. Moreover, LPL−/− mice developed much less severe neurologic symptoms in experimental autoimmune encephalomyelitis, which correlated with impaired T cell responses to Ag, manifested by reduced proliferation and production of IFN-γ and IL-17. Thus, LPL-dependent actin bundling facilitates the formation of lamellipodia and normal immunological synapses and thereby enables T cell activation.

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“…These two human cell type-specific isoforms, L-and T-plastin (80% amino acid identity), are expressed in hematopoietic cells and in cells derived from solid tissue, respectively [9] . In 1990, it was observed that an amino-terminal sequence containing a potential calcium binding domain was missing in the sequences reported earlier [10,11] . A third human plastin isoform, called I-plastin, was discovered as a polypeptide that is specifically expressed in the small intestine, colon and kidney, and is 86% identical to the chicken fimbrin (plastin) isoform [12,13] .…”

Section: Discoverymentioning

confidence: 97%

Plastins: versatile modulators of actin organization in (patho)physiological cellular processes

Delanote

Vandekerckhove

Gettemans

2005

Acta Pharmacologica Sinica

148

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Many actin-binding proteins are expressed in eukaryotic cells. These polypeptides assist in stabilizing and rearranging the organization of the actin cytoskeleton in response to external stimuli, or during cell migration and adhesion. Here we review a particular set of actin-binding proteins called plastins. Plastins (also called fimbrins) belong to a subclass of actin-binding proteins known as actin bundling proteins. Three isoforms have been characterized in mammals: T-plastin is expressed in cells from solid tissue, whereas L-plastin occurs predominantly in hematopoietic cells. The third isoform, I-plastin, is specifically expressed in the small intestine, colon and kidney. These proteins share the unique property of cross-linking actin filaments into tight bundles. Although plastins are primarily involved in regulation of the actin cytoskeleton, they possess some unique features. For instance, they are implicated in invasion by pathogenic bacteria such as Shigella flexneri and Salmonella typhimurium. Also, L-plastin plays an important role in leukocyte function. T-plastin, on the other hand, is possibly involved in DNA repair. Finally, both T-and L-plastin are implicated in several diseases, and L-plastin is considered to be a valuable marker for cancer.

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65-Kilodalton protein phosphorylated by interleukin 2 stimulation bears two putative actin-binding sites and two calcium-binding sites

Cited by 28 publications

References 34 publications

L-Plastin Regulates Polarization and Migration in Chemokine-Stimulated Human T Lymphocytes

L-Plastin Regulates Polarization and Migration in Chemokine-Stimulated Human T Lymphocytes

Actin-Bundling Protein L-Plastin Regulates T Cell Activation

Plastins: versatile modulators of actin organization in (patho)physiological cellular processes

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