{"id":60191,"date":"2026-04-01T06:54:47","date_gmt":"2026-04-01T04:54:47","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/04\/01\/basal-phosphorylation-of-ship1-by-lyn-suppresses-proinflammatory-signaling-in-the-absence-of-a-phagocytic-synapse\/"},"modified":"2026-04-01T06:54:47","modified_gmt":"2026-04-01T04:54:47","slug":"basal-phosphorylation-of-ship1-by-lyn-suppresses-proinflammatory-signaling-in-the-absence-of-a-phagocytic-synapse","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/04\/01\/basal-phosphorylation-of-ship1-by-lyn-suppresses-proinflammatory-signaling-in-the-absence-of-a-phagocytic-synapse\/","title":{"rendered":"Basal phosphorylation of SHIP1 by Lyn suppresses proinflammatory signaling in the absence of a phagocytic synapse"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Mar 17;215(3):vkaf372. doi: 10.1093\/jimmun\/vkaf372.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Microscale engagement of the hemi-immunoreceptor tyrosine-based activation motif-containing receptor Dectin-1 by fungal particles activates Src-family kinases (SFKs) and Syk, drives second-messenger generation, and induces downstream Erk and Akt signaling and proinflammatory responses in macrophages. To avoid inappropriate activation in the absence of a pathogenic threat, macrophages restrict signaling in response to low-valency ligands. To examine how SFKs regulate this sensitivity threshold, we compared signaling induced by pharmacological SFK activation with signaling triggered by depleted zymosan, a high-valency \u03b2-glucan particle that engages Dectin-1 to form a phagocytic synapse. We found that particulate engagement of Dectin-1 protected the inhibitory ITIM-associated phosphatase SHIP1 from phosphorylation by SFKs, allowing robust activation of Erk and Akt and proinflammatory induction. In contrast, receptor-independent SFK activation induced phosphorylation of SHIP1 and failed to amplify signaling downstream of PLC\u03b32 and PI3K. Although multiple SFKs could phosphorylate SHIP1, Lyn uniquely maintained the basal set-point of SHIP1 phosphorylation, thereby keeping PIP3 levels low and suppressing basal Erk and Akt signaling. This Lyn-dependent regulation was essential for suppressing Akt activation and balancing signaling through the Erk and Akt pathways in the absence of a phagocytic synapse. In contrast, antimicrobial responses to particulate stimuli, including second-messenger signaling, Erk\/Akt, and proinflammatory outputs, did not strictly require Lyn expression. These findings highlight the unique role of Lyn in limiting spurious proinflammatory signaling and shed light on a mechanism by which macrophages selectively respond to high-valency particulate ligands that override this basal inhibitory program.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41916428\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260401005446&amp;v=2.19.0.post6+133c1fe\">41916428<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf372\">10.1093\/jimmun\/vkaf372<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Mar 17;215(3):vkaf372. doi: 10.1093\/jimmun\/vkaf372. ABSTRACT Microscale engagement of the hemi-immunoreceptor tyrosine-based activation motif-containing receptor Dectin-1 by fungal particles activates Src-family kinases (SFKs) and Syk, drives second-messenger generation, and induces downstream Erk and Akt signaling and proinflammatory responses in macrophages. To avoid inappropriate activation in the absence of a pathogenic threat, macrophages restrict &#8230; <a title=\"Basal phosphorylation of SHIP1 by Lyn suppresses proinflammatory signaling in the absence of a phagocytic synapse\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/04\/01\/basal-phosphorylation-of-ship1-by-lyn-suppresses-proinflammatory-signaling-in-the-absence-of-a-phagocytic-synapse\/\" aria-label=\"Read more about Basal phosphorylation of SHIP1 by Lyn suppresses proinflammatory signaling in the absence of a phagocytic synapse\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-60191","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/60191","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=60191"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/60191\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=60191"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=60191"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=60191"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}