Appearance of membrane-bound tyrosine kinase during differentiation of HL-60 leukemia cells by immune interferon and tumor necrosis factor

Glazer, Robert I.; Chapekar, Mrunal S.; Hartman, Kathleen D.; Knode, Marian C.

doi:10.1016/0006-291x(86)90721-7

Cited by 19 publications

(2 citation statements)

References 20 publications

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“…Stimulation of c-fes autophosphorylation in vivo may induce interaction with GAP, resulting in altered p21ras function.The human c-fes gene encodes a 93-kDa PTK1 (p93c'^cj) that is expressed predominantly in myeloid cells of the granulocytic and monocytic lineages (Feldman et al, 1985;MacDonald et al, 1985;Smithgall et al, 1988). p93c'7" tyrosine kinase activity is greatly enhanced during the differentiation of human myeloid leukemia cell lines in vitro, suggestive of an active role for p9¥~fes during myeloid development Glazer et al, 1986). Further support for this hypothesis comes from gene-transfer studies with K562 myeloid leukemia cells, a differentiationresistant cell line that does not express c-fes (Lozzio et al, 1981).…”

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confidence: 99%

Phosphorylation of the ras GTPase-activating protein (GAP) by the p93c-fes protein-tyrosine kinase in vitro and formation of GAP-fes complexes via an SH2 domain-dependent mechanism

Hjermstad¹,

Briggs²,

Smithgall³

1993

Biochemistry

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The protein-tyrosine kinase encoded by the human c-fes protooncogene (p93c-fes) plays a direct role in myeloid differentiation, but downstream substrates for this kinase have not been identified. Here we report that the human ras GTPase-activating protein (GAP) is a substrate for p93c-fes in vitro. Purified, recombinant GAP was readily phosphorylated on tyrosine residues by bacterially-expressed p93c-fes. Two-dimensional tryptic mapping revealed a single GAP phosphopeptide, consistent with specific phosphorylation of GAP by p93c-fes on one or several closely-spaced tyrosine residues. Autophosphorylated p93c-fes also formed a stable complex with GAP. Complex formation is likely to involve the src homology 2 (SH2) domains of GAP and autophosphorylated tyrosine residues of p93c-fes, as deletion of the fes SH2 domain did not abolish complex formation. Furthermore, immobilized recombinant fusion proteins containing either or both of the GAP SH2 domains were able to precipitate p93c-fes with an affinity equal to that observed with a monoclonal antibody against the recombinant fes protein. Fusion proteins containing the GAP N-terminal, C-terminal catalytic, or SH3 domains did not bind to p93c-fes. Interaction of the GAP SH2 domains with p93c-fes is phosphorylation-dependent, as the recombinant SH2 domain proteins were unable to bind to a kinase-defective c-fes mutant and showed reduced binding of a mutant in which one of the two tyrosine autophosphorylation sites was replaced with phenylalanine. Stimulation of c-fes autophosphorylation in vivo may induce interaction with GAP, resulting in altered p21ras function.

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confidence: 99%

Phosphorylation of the ras GTPase-activating protein (GAP) by the p93c-fes protein-tyrosine kinase in vitro and formation of GAP-fes complexes via an SH2 domain-dependent mechanism

Hjermstad¹,

Briggs²,

Smithgall³

1993

Biochemistry

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“…Small samplings of patients' cells showed that myeloid leukemias express greater levels of c-fes mRNA than lymphocytic leukemias or lymphomas (Slamon et al, 1984;Ferrari et al, 1985). Moreover, in leukemic cell lines, c-fes mRNA (Ferrari et al, 1985;Lanfrancone et al, 1989), protein levels (Yates et al, 1995), and kinase activity (Glazer et al, 1986;Yu and Glazer, 1987;Smithgall et al, 1988), increase upon induction of granulocyte differentiation.…”

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confidence: 91%

Expression of c-Fes Protein Isoforms Correlates with Differentiation in Myeloid Leukemias

Carlson¹,

McAdara²,

Browning³

et al. 2005

DNA and Cell Biology

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The cellular fes gene encodes a 93-kilodalton protein-tyrosine kinase (p93) that is expressed in both normal and neoplastic myeloid cells. Increased c-Fes expression is associated with differentiation in normal myeloid cells and cell lines. Our hypothesis was that primary leukemia cells would show a similar pattern of increased expression in more differentiated cells. Therefore, we compared c-Fes expression in cells with an undifferentiated, blast phenotype (acute myelogenous leukemia--AML) to cells with a differentiated phenotype (chronic myelogenous leukemia--CML). Instead of differences in p93 expression levels, we found complex patterns of c-Fes immunoreactive proteins that corresponded with differentiation in normal and leukemic myeloid cells. The "blast" pattern consisted of c-Fes immunoreactive proteins p93, p74, and p70; the "differentiated" pattern showed two additional c-Fes immunoreactive proteins, p67 and p62. Using mRNA from mouse and human cell lines, we found deletion of one or more exons in the c-fes mRNA. Those deletions predicted truncation of conserved domains (CDC15/FCH and SH2) involved in protein-protein interactions. No deletions were found, however, within the kinase domain. We infer that alternative splicing generates a family of c-Fes proteins. This may be a mechanism to direct the c-Fes kinase domain to different subcellular locations and/or substrates at specific stages of myeloid cell differentiation.

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Truncation of c-fes via Gene Targeting Results in Embryonic Lethality and Hyperproliferation of Hematopoietic Cells

Hackenmiller

Simon

2002

Developmental Biology

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The c-fes protooncogene encodes a nonreceptor tyrosine kinase (Fes) implicated in cytokine receptor signal transduction, granulocyte survival, and myeloid differentiation. To study the role of c-fes during myelopoiesis, we generated embryonic stem (ES) cells with a targeted disruption of the c-fes locus. Targeted mutagenesis deletes the C-terminal SH2 and tyrosine kinase domains of c-fes (referred to as c-fes(Delta c/Delta c)). We demonstrate that the c-fes(Delta c/Delta c) allele results in a truncated Fes protein that retains the N-terminal oligomerization domain, but lacks both the SH2 and the tyrosine kinase domain. In vitro differentiation of c-fes(Delta c/Delta c) ES cells results in hyperproliferation of an early myeloid cell. Generation of c-fes(Delta c/Delta c) mutant chimeric mice causes lethality by E13.5 with embryos exhibiting pleiotropic defects, the most striking being cardiovascular abnormalities. These results establish that c-fes is an important regulator of myeloid cell proliferation and embryonic development.

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Appearance of membrane-bound tyrosine kinase during differentiation of HL-60 leukemia cells by immune interferon and tumor necrosis factor

Cited by 19 publications

References 20 publications

Phosphorylation of the ras GTPase-activating protein (GAP) by the p93c-fes protein-tyrosine kinase in vitro and formation of GAP-fes complexes via an SH2 domain-dependent mechanism

Phosphorylation of the ras GTPase-activating protein (GAP) by the p93c-fes protein-tyrosine kinase in vitro and formation of GAP-fes complexes via an SH2 domain-dependent mechanism

Expression of c-Fes Protein Isoforms Correlates with Differentiation in Myeloid Leukemias

Truncation of c-fes via Gene Targeting Results in Embryonic Lethality and Hyperproliferation of Hematopoietic Cells

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