title: Expression and subcellular localization of Spred proteins in mouse and human tissues.
abstract: Spred-1 and Spred-2 (Sprouty-related protein with an EVH1 domain) are recently described members of the EVH1 (Ena/VASP-homology domain 1) family. Both Spred-1 and Spred-2 are membrane-associated substrates of receptor tyrosine kinases and they act as negative regulators of the Ras pathway upon growth factor stimulation. Since the Spred family members seem to exert overlapping molecular functions, the isotype-specific function of each member remains enigmatic. To date, no comprehensive expression profiling of Spred proteins has been shown. Therefore, we compared mRNA and protein expression patterns of Spred-1 and Spred-2 systematically in mouse organs. Furthermore, we focused on the tissue-specific expression of Spred-2 in adult human tissues, the subcellular localization, and the potential role of Spred-2 in the organism. Our studies show that expression patterns of Spred-1 and Spred-2 differ markedly among various tissues and cell types. In mouse, Spred-1 and Spred-2 were found to be expressed predominantly in brain, whereas Spred-2 was found to be more widely expressed in various adult tissues than Spred-1. In humans, Spred-2 was found to be strongly expressed in glandular epithelia and, at the subcellular level, its immunoreactivity was associated with secretory vesicles. Using confocal microscopy we found Spred-2 to be strongly colocalized with Rab11 and, to a lesser extent, with Rab5a GTPase, an observation that was not made for Spred-1. We conclude that the two members of the recently discovered Spred protein family, Spred-1 and Spred-2, show a highly specific expression pattern in various tissues reflecting a specific physiological role for the individual Spred isoforms in these tissues. Furthermore, it becomes most likely that Spred-2 is involved in the regulation of secretory pathways.
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080 Wuerzburg, Germany.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Engelhardt
authors.forename: Karin
authors.initials: K
authors.lastname: Bundschu
authors.forename: Marlies
authors.initials: M
authors.lastname: Messerschmitt
authors.forename: Thomas
authors.initials: T
authors.lastname: Renné
authors.forename: Ulrich
authors.initials: U
authors.lastname: Walter
authors.forename: Matthias
authors.initials: M
authors.lastname: Reinhard
authors.forename: Kai
authors.initials: K
authors.lastname: Schuh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001921:Brain / Q000378:metabolism; D003656:Decidua / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism; D011247:Pregnancy; D012097:Repressor Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000378:metabolism / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D012097:Repressor Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C500760:SPRED2 protein, human; C433763:Spred1 protein, mouse; C433764:Spred2 protein, mouse