{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Jing Yang"],"species":["Homo Sapiens"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0017583000"],"submitter_email":["yangjing54@hotmail.com"],"submitter_affiliation":["National Center for Protein Sciences (Beijing)"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"pubmed_abstract":["<h4>Introduction</h4>Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular pattern recognition receptor that detects bacterial peptidoglycan and initiates innate immune responses through membrane-associated signaling complexes. NOD1 activation depends on ZDHHC5-mediated palmitoylation, which promotes its membrane recruitment. However, whether growth factors and insulin modulate this NOD1 activation remains poorly defined.<h4>Methods</h4>We investigated the effects of growth factors and insulin on NOD1 signaling using biochemical and cell-based approaches. Protein phosphorylation and interactions were analyzed by immunoblotting, co-immunoprecipitation, and mutagenesis assays. NOD1 palmitoylation, membrane localization, and downstream signaling activities were evaluated following modulation of AKT signaling and ZDHHC5 phosphorylation.<h4>Results</h4>We found that growth factors and insulin positively regulate NOD1 activation through an AKT-ZDHHC5-NOD1 signaling axis. Mechanistically, AKT directly phosphorylated the palmitoyltransferase ZDHHC5 at Ser345 and Ser380, promoting its retention at the plasma membrane and enhancing its enzymatic activity toward NOD1. AKT-dependent phosphorylation increased NOD1 palmitoylation and membrane recruitment, thereby facilitating activation of downstream innate immune signaling pathways.<h4>Discussion</h4>These findings identify a previously unrecognized mechanism linking growth factor- and insulin-mediated AKT activation to innate immune signaling. AKT-dependent phosphorylation of ZDHHC5 promotes NOD1 palmitoylation and activation, revealing a positive regulatory axis that integrates metabolic cues with innate immune responses. The AKT-ZDHHC5 pathway may therefore represent a potential target for modulating NOD1- driven inflammatory diseases."],"pubmed_title":["AKT-mediated phosphorylation of ZDHHC5 promotes NOD1 palmitoylation and innate immune signaling."],"pubmed_authors":["Mi Shaojie S, Zhu Yue Y, Li Qian Q, Wang Xin X, Guo Xuewu X, Chen Yali Y"],"additional_accession":[]},"is_claimable":false,"name":"AKT-mediated phosphorylation of ZDHHC5","description":"In this project, we affinity-purified FLAG-ZDHHC5 from HEK293T cells co-expressing MYR-HA-AKT and subjected to mass spectrometry analysis. Three phosphopeptides derived from ZDHHC5 were identified.","dates":{"publication":"Tue Jun 02 00:00:00 BST 2026"},"accession":"PXD079175","cross_references":{"TAXONOMY":["9606"],"pubmed":["42344932"]}}