@article{51feb8565f1b4a9c94c954d5a093c332,
title = "HS1 Functions as an Essential Actin-Regulatory Adaptor Protein at the Immune Synapse",
abstract = "HS1, the leukocyte-specific homolog of cortactin, regulates F-actin in vitro and is phosphorylated in response to TCR ligation, but its role in lymphocyte activation has not been addressed. We demonstrate that HS1-deficient T cells fail to accumulate F-actin at the immune synapse (IS) and, upon TCR ligation, form actin-rich structures that are disordered and unstable. Early TCR activation events are intact in these cells, but Ca2+ influx and IL-2 gene transcription are defective. Importantly, HS1 tyrosine phosphorylation is required for its targeting to the IS and for its function in regulating actin dynamics and IL-2 promoter activity. Phosphorylation also links HS1 to multiple signaling proteins, including Lck, PLCγ1, and Vav1, and is essential for the stable recruitment of Vav1 to the IS. Taken together, our studies show that HS1 is indispensable for signaling events leading to actin assembly and IL-2 production during T cell activation.",
keywords = "MOLIMMUNO, SIGNALING",
author = "Gomez, {Timothy S.} and McCarney, {Sean D.} and Esteban Carrizosa and Labno, {Christine M.} and Comiskey, {Erin O.} and Nolz, {Jeffrey C.} and Peimin Zhu and Freedman, {Bruce D.} and Clark, {Marcus R.} and Rawlings, {David J.} and Billadeau, {Daniel D.} and Burkhardt, {Janis K.}",
note = "Funding Information: This work was supported by the Mayo Foundation, a Cancer Research Institute Investigator award, and NIH grant R01-AI065474 to D.D.B., by NIH grant F31-AI068624 to T.S.G., by a Leukemia and Lymphoma Scholar Award and NIH grant HD37091 to D.J.R., and by R01-AI44835 and a grant with the Pennsylvania Department of Health to J.K.B. The Pennsylvania Department of Health disclaims responsibility for any analyses, interpretations, or conclusions. We thank Shuixing Li and Renell Morgan for technical assistance, Morris Birnbaum and Edward Williamson for access to and assistance with spinning disk confocal microscopy, Mark Roden (3I) for help with morphometry, and Lynn Spruce and Mike Rosenblatt (CHOP Protein Core) for help with Mass Spectrometry. The authors declare that they have no competing financial interests. ",
year = "2006",
month = jun,
doi = "10.1016/j.immuni.2006.03.022",
language = "English (US)",
volume = "24",
pages = "741--752",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "6",
}