Expression and subcellular localization of Spred proteins in mouse and human tissues

TY - JOUR

T1 - Expression and subcellular localization of Spred proteins in mouse and human tissues

AU - Engelhardt, Catherine M

AU - Bundschu, Karin

AU - Messerschmitt, Marlies

AU - Renné, Thomas

AU - Walter, Ulrich

AU - Reinhard, Matthias

AU - Schuh, Kai

PY - 2004/12/1

Y1 - 2004/12/1

N2 - 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.

AB - 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.

KW - Animals

KW - Antibody Formation

KW - Antibody Specificity

KW - Brain

KW - Decidua

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Developmental

KW - Humans

KW - Liver

KW - Lung

KW - MAP Kinase Signaling System

KW - Male

KW - Mice

KW - Microscopy, Confocal

KW - Myocardium

KW - Pregnancy

KW - Repressor Proteins

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Testis

KW - rab GTP-Binding Proteins

U2 - 10.1007/s00418-004-0725-6

DO - 10.1007/s00418-004-0725-6

M3 - SCORING: Journal article

C2 - 15580519

VL - 122

SP - 527

EP - 538

JO - HISTOCHEM CELL BIOL

JF - HISTOCHEM CELL BIOL

SN - 0948-6143

IS - 6

ER -