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Identification and characterization of human and murine c-fes proteins MacDonald, Ian Andrew


The c-fes and c-fps genes are, respectively, the mammalian and avian proto-oncogenes which were ancestral to the retroviral fps/fes oncogenes. While the proteins encoded by c-fps/fes proto-oncogenes had been identified in a number of species the homologous proteins had not been isolated or characterized in human or murine cells. This study was undertaken in an attempt to identify c-fps/fes proteins in human and murine cells Using a cross-reactive rat anti-v-fps serum two immunologically cross-reactive proteins of M[sub r] 92,000 (p92) and 94,000 (p94) were immunoprecipitated from a variety of human and murine cells. Functional studies indicated that both of these proteins possessed protein kinase activity and were able to autophosphorylate and to phosphorylate exogenous substrates at tyrosine residues. Structural comparisons suggested that p92 was very closely related in primary sequence to the v-fes protein P85[See Thesis for protein] while p94 was more distantly related. On the basis of immunological cross-reactivity, intrinsic protein-tyrosine kinase activity, and structural relatedness it was concluded that p92 represents the human and murine c-fes gene product; p94, while possessing some similarities, is probably not a c-fes protein but is likely a related protein-tyrosine kinase. Examination of human and murine cells and cell lines revealed that the expression of c-fes was confined to those of hemopoietic origin and especially to those cells belonging to myeloid lineages. The expression of c-fes was investigated in human myeloid leukemia cell lines during exposure to a chemical inducer of differentiation; complex patterns of expression were observed and these are discussed. The expression of c-fes appears to be differentially regulated in responsive and unresponsive cells and it is possible that it plays a role in committment to myeloid lineages.

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