title: The human eps15 gene, encoding a tyrosine kinase substrate, is conserved in evolution and maps to 1p31-p32.
abstract: Employing an expression cloning approach for tyrosine kinase substrates, we have previously isolated the coding sequence for a novel putative EGFR substrate, eps15, from NIH3T3 fibroblasts. Eps15 displayed a receptor-specific pattern of tyrosine phosphorylation in vivo and was able to transform NIH3T3 cells upon overexpression. To gain understanding of eps15 function as well as its role in normal and neoplastic proliferation, we cloned the human eps15 coding sequence and studied expression of the human RNA and protein, evolutionary conservation, and chromosomal location. The close structural similarity of human eps15 with the murine homologue is indicated by 89% and 90% identity of nucleotide and predicted amino acid sequences, respectively. Using the human eps15 coding sequence as probe, we demonstrate that eps15 is member of a gene family that is highly conserved during evolution. An essential function of eps15 in cell growth regulation is underscored by our observation of ubiquitous expression at the transcript and the protein level in normal and malignant human cells. The human EPS15 locus maps to chromosome 1p31-p32, a region involved in deletion in neuroblastoma, translocations in acute lymphoblastic leukemia, and exhibiting a fragile site.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: W T
authors.initials: WT
authors.lastname: Wong
authors.forename: M H
authors.initials: MH
authors.lastname: Kraus
authors.forename: F
authors.initials: F
authors.lastname: Carlomagno
authors.forename: A
authors.initials: A
authors.lastname: Zelano
authors.forename: T
authors.initials: T
authors.lastname: Druck
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.forename: K
authors.initials: K
authors.lastname: Huebner
authors.forename: P P
authors.initials: PP
authors.lastname: Di Fiore
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000737:chemistry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; C486206:EPS15 protein, human; C082729:Eps15 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins