title: A Central Nervous System-Dependent Intron-Embedded Gene Encodes a Novel Murine Fyn Binding Protein.
abstract: The interplay between the nervous and immune systems is gradually being unraveled. We previously reported in the mouse the novel soluble immune system factor ISRAA, whose activation in the spleen is central nervous system-dependent. We also showed that ISRAA plays a role in modulating anti-infection immunity. Herein, we report the genomic description of the israa locus, along with some insights into the structure-function relationship of the protein. Our findings revealed that israa is nested within intron 6 of the mouse zmiz1 gene. Protein sequence analysis revealed a typical SH2 binding motif (Y102TEV), with Fyn being the most likely binding partner. Docking simulation showed a favorable conformation for the ISRAA-Fyn complex, with a specific binding mode for the binding of the YTEV motif to the SH2 domain. Experimental studies showed that in vitro, recombinant ISRAA is phosphorylated by Fyn at tyrosine 102. Cell transfection and pull-down experiments revealed Fyn as a binding partner of ISRAA in the EL4 mouse T-cell line. Indeed, we demonstrated that ISRAA downregulates T-cell activation and the phosphorylation of an activation tyrosine (Y416) of Src-family kinases in mouse splenocytes. Our observations highlight ISRAA as a novel Fyn binding protein that is likely to be involved in a signaling pathway driven by the nervous system.
authors.affiliation: College of Postgraduate Studies, Arabian Gulf University, Manama, Bahrain.|HH Al-Jawhara Centre for Molecular Medicine and Inherited Diseases, Manama, Bahrain.
authors.forename: Noureddine
authors.initials: N
authors.lastname: Ben Khalaf
authors.affiliation: HH Al-Jawhara Centre for Molecular Medicine and Inherited Diseases, Manama, Bahrain.
authors.forename: Safa
authors.initials: S
authors.lastname: Taha
authors.affiliation: HH Al-Jawhara Centre for Molecular Medicine and Inherited Diseases, Manama, Bahrain.
authors.forename: Moiz
authors.initials: M
authors.lastname: Bakhiet
authors.affiliation: College of Postgraduate Studies, Arabian Gulf University, Manama, Bahrain.
authors.forename: M Dahmani
authors.initials: MD
authors.lastname: Fathallah
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007438:Introns; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000502:physiology*; D018909:src Homology Domains
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C528563:Zimp10 protein, mouse; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn