Evolutionary conservation of the EPS8 gene and its mapping to human chromosome 12q23-q24.
We have previously isolated the coding sequence for a novel substrate for tyrosine kinases, eps8, from NIH3T3 fibroblasts. Eps8 was phosphorylated in vivo by several receptor tyrosine kinases (RTKs) and, upon overexpression, was able to enhance EGFR-mediated mitogenic signaling in NIH3T3 cells. To gain understanding of eps8 function as well as its role in normal and neoplastic proliferation, we cloned the human eps8 coding sequence and studied expression of the human RNA and protein, evolutionary conservation, and chromosomal location. In addition to a previously identified SH3 domain, the predicted amino acid sequence of human eps8 revealed a non-random distribution of prolines, clustered in a way to suggest SH3-binding sites and a putative PH domain. Eps8 was expressed in all epithelial and fibroblastic lines examined and in some, but not all, hematopoietic cells. An essential function of eps8 in cell growth regulation was underscored by its conservation during evolution, where eps8-related sequences were detected as early as in Saccharomyces cerevisiae. Finally, the human EPS8 locus was mapped to chromosome 12q23-q24.
Wong
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WT
Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Carlomagno
F
F
Druck
T
T
Barletta
C
C
Croce
C M
CM
Huebner
K
K
Kraus
M H
MH
Di Fiore
P P
PP
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C489989:EPS8 protein, human; C083430:Eps8 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins