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oai:figshare.com:article/33315468 2026-09-30T23:28:51Z category_35552 category_30881 category_30884 category_30911 portal_234 item_type_6 month_year_09_2026

The discovery of hidden guanylate cyclases (GCs) in the <i>Homo sapiens</i> proteome Ilona Turek (9478139) Lubna Freihat (24614619) Jignesh Vyas (24614625) Janet Wheeler (9493463) Victor Muleya (14710042) David T Manallack (24614622) Chris Gehring (10582) Helen Irving (8310519) Applied computing Biological sciences Biochemistry and cell biology Proteomics and intermolecular interactions (excl. medical proteomics) Crypto guanylate cyclase Cyclic GMP (cGMP) Neurotropic receptor tyrosine kinase 1 (NTRK1) Phytosulfokine receptor 1 (PSKR1) Tyrosine receptor kinase A (TrkA) <p dir="ltr">Recent discoveries have established functional guanylate cyclase (GC) catalytic centers with low activity within kinase domains in plants. These crypto GCs generate guanosine 3’,5’-cyclic monophosphate (cGMP) essential for both intramolecular and downstream signaling. Here, we have set out to search for such crypto GCs moonlighting in kinases in the <i>H. sapiens</i> proteome and identified 18 candidates, including the neurotropic receptor tyrosine kinase 1 (NTRK1). NTRK1 shows a domain architecture much like plant receptor kinases such as the phytosulfokine receptor, where a functional GC essential for downstream signaling is embedded within a kinase domain. In vitro characterization of the NTRK1 shows that the embedded NTRK1 GC is functional with a marked preference for Mn²⁺ over Mg²⁺. This therefore points to hitherto unsuspected roles of cGMP in intramolecular and downstream signaling of NTRK1 and the role of cGMP in NTRK1-dependent growth and neoplasia.</p> 2023-11-09T00:00:00Z Text Journal contribution 10.1016/j.csbj.2023.11.005 https://figshare.com/articles/journal_contribution/The_discovery_of_hidden_guanylate_cyclases_GCs_in_the_i_Homo_sapiens_i_proteome/33315468 CC BY 4.0