{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:01:51Z","timestamp":1792882911326,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T00:00:00Z","timestamp":1667001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CTSA TL1","award":["TR000155"],"award-info":[{"award-number":["TR000155"]}]},{"name":"CTSA TL1","award":["R01 HD60723"],"award-info":[{"award-number":["R01 HD60723"]}]},{"name":"CTSA TL1","award":["5K12 HD001271"],"award-info":[{"award-number":["5K12 HD001271"]}]},{"name":"UC SOM Department Obstetrics &amp; Gynecology (VDW)","award":["TR000155"],"award-info":[{"award-number":["TR000155"]}]},{"name":"UC SOM Department Obstetrics &amp; Gynecology (VDW)","award":["R01 HD60723"],"award-info":[{"award-number":["R01 HD60723"]}]},{"name":"UC SOM Department Obstetrics &amp; Gynecology (VDW)","award":["5K12 HD001271"],"award-info":[{"award-number":["5K12 HD001271"]}]},{"name":"March of Dimes Basil O\u2019Conner (VDW)","award":["TR000155"],"award-info":[{"award-number":["TR000155"]}]},{"name":"March of Dimes Basil O\u2019Conner (VDW)","award":["R01 HD60723"],"award-info":[{"award-number":["R01 HD60723"]}]},{"name":"March of Dimes Basil O\u2019Conner (VDW)","award":["5K12 HD001271"],"award-info":[{"award-number":["5K12 HD001271"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Preeclampsia is a pregnancy-specific disorder involving placental abnormalities. Elevated placental Sialic acid immunoglobulin-like lectin (Siglec)-6 expression has been correlated with preeclampsia. Siglec-6 is a transmembrane receptor, expressed predominantly by the trophoblast cells in the human placenta. It interacts with sialyl glycans such as sialyl-TN glycans as well as binds leptin. Siglec-6 overexpression has been shown to influence proliferation, apoptosis, and invasion in the trophoblast (BeWo) cell model. However, there is no direct evidence that Siglec-6 plays a role in preeclampsia pathogenesis and its signaling potential is still largely unexplored. Siglec-6 contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an ITIM-like motif in its cytoplasmic tail suggesting a signaling function. Site-directed mutagenesis and transfection were employed to create a series of Siglec-6 expressing HTR-8\/SVneo trophoblastic cell lines with mutations in specific functional residues to explore the signaling potential of Siglec-6. Co-immunoprecipitation and inhibitory assays were utilized to investigate the association of Src-kinases and SH-2 domain-containing phosphatases with Siglec-6. In this study, we show that Siglec-6 is phosphorylated at ITIM and ITIM-like domains by Src family kinases. Phosphorylation of both ITIM and ITIM-like motifs is essential for the recruitment of phosphatases like Src homology region 2 containing protein tyrosine phosphatase 2 (SHP-2), which has downstream signaling capabilities. These findings suggest Siglec-6 as a signaling molecule in human trophoblasts. Further investigation is warranted to determine which signaling pathways are activated downstream to SHP-2 recruitment and how overexpression of Siglec-6 in preeclamptic placentas impacts pathogenesis.<\/jats:p>","DOI":"10.3390\/cells11213427","type":"journal-article","created":{"date-parts":[[2022,10,29]],"date-time":"2022-10-29T23:45:00Z","timestamp":1667087100000},"page":"3427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Siglec-6 Signaling Uses Src Kinase Tyrosine Phosphorylation and SHP-2 Recruitment"],"prefix":"10.3390","volume":"11","author":[{"given":"Adrianne L.","family":"Stefanski","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of Colorado, Aurora, CO 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Renecle","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of Colorado, Aurora, CO 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of Colorado, Aurora, CO 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpi","family":"Sehgal","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purnima","family":"Narasimhan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen K.","family":"Rumer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of Colorado, Aurora, CO 80309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1136-2907","authenticated-orcid":false,"given":"Virginia D","family":"Winn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, University of Colorado, Aurora, CO 80309, USA"},{"name":"Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev-pathol-121808-102149","article-title":"Pathogenesis of preeclampsia","volume":"5","author":"Young","year":"2010","journal-title":"Annu. 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