Reassessment of the v-fms sequence: threonine phosphorylation of the COOH-terminal domain

Smola, U; Hennig, Dagmar; Hadwiger-Fangmeier, A.; Schütz, Burkhard; Pfaff, Eberhard; Niemann, Heiner; Tamura, Teruko

doi:10.1128/jvi.65.11.6181-6187.1991

Cited by 6 publications

(2 citation statements)

References 32 publications

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“…The v-fms oncogene product encoded by Suzan McDonough feline sarcoma virus differs from the c-fms feline protein by eight scattered single-amino-acid substitutions (10,45,56). In addition, 14 unrelated residues are substituted for the 50 carboxy-terminal aa of the fms protein, removing a C-terminal tyrosine (Tyr-969 in the cat sequence) whose phosphorylation might negatively regulate the receptor kinase activity (45,56). In order to detect eventual additional c-fms sequence alterations, we sequenced the seven proviruses downstream from the 3Ј primer up to the end of the coding sequence.…”

Section: Transforming Potentials Of Viruses With Deletions and Analysmentioning

confidence: 99%

Isolation of new oncogenic forms of the murine c-fms gene

Parseval

Bordereaux

Varlet

et al. 1995

J Virol

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The c-fms gene encodes the receptor for the macrophage colony-stimulating factor, which plays a key role in the proliferation and differentiation of cells of the myelomonocytic lineage. In order to study the effects of overexpression of the macrophage colony-stimulating factor receptor in hematopoietic cells, a Harvey sarcoma virus-derived retroviral vector containing the murine c-fms cDNA was pseudotyped with Friend murine leukemia virus and inoculated into newborn DBA/2 mice. This viral complex induced monoclonal or oligoclonal leukemias with a shorter latency than that for Friend murine leukemia virus alone. Unexpectedly, 60% of the integrated fms proviruses had deletions at the 5 end of the c-fms gene. Sequence analysis of seven mutant proviruses indicated that the deletions always included the c-fms ligand binding domain and either occurred within the c-fms sequences, leaving the fms open reading frame unchanged, or joined VL30 sequences located at the 5 end of the parental retroviral vector to internal c-fms sequences, resulting in truncated fms proteins devoid of the canonical signal peptide. In contrast to all tyrosine kinase receptors transduced in retroviruses, no helper gag-or env-derived sequences were fused to the rearranged fms sequences. Viral supernatants isolated from hematopoietic tumors with viruses with deletions were able to transform NIH 3T3 cells as efficiently as parental fms virus, indicating that deletions resulted in constitutive activation of the c-fms gene. These oncogenic variants differ from those transduced in the Suzan McDonough strain of feline sarcoma viruses (L. Donner, L. A. Fedele, C. F. Garon, S. J. Anderson, and C. J. Sherr, J. Virol . 41:489-500, 1982). The high rate of c-fms rearrangement and its relevance in the occurrence of hematopoietic tumors are discussed.

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Section: Transforming Potentials Of Viruses With Deletions and Analysmentioning

confidence: 99%

Isolation of new oncogenic forms of the murine c-fms gene

Parseval

Bordereaux

Varlet

et al. 1995

J Virol

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“…The v-fms oncogene of feline sarcoma virus encodes a modified receptor tyrosine kinase that differs only in seven amino acid positions and in the C-terminal sequence from the cellular receptor for macrophage colony-stimulating factor (M-CSF) (14,43,44,55). Both proteins contain a large extracellular domain that binds M-CSF and a cytoplasmic tyrosine kinase domain, split by an insertion of approximately 70 amino acids, termed the kinase insert region.…”

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confidence: 99%

Tyrosine 807 of the v-Fms oncogene product controls cell morphology and association with p120RasGAP

Trouliaris

Smola

Chang

et al. 1995

J Virol

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Expression of the v-fms oncogene of feline sarcoma virus in fibroblasts causes surface exposure of an activated receptor tyrosine kinase, v-Fms, that is autophosphorylated at multiple sites within its cytoplasmic domain. Cellular proteins interacting with this part of v-Fms modulate the mitogenic activity and morphology of the cells. We show here that the tyrosine residue in position 807 (Y-807) of the v-Fms molecule constitutes a major autophosphorylation site. The replacement of this residue by phenylalanine (Y807F mutation) allowed us to functionally dissect v-Fms-specific mitogenic and morphogenic cascades. Cells expressing the mutant v-Fms molecule resembled wild-type (wt) v-Fms-transformed (wt-v-Fms) cells in terms of [ 3 H]thymidine uptake rates and activation of the Ras/Raf-1 mitogenic cascade. Such cells showed, however, a flat morphology and contained intact actin cables and fibronectin network. Our studies indicate that the v-Fms molecule controls cell morphology by a cascade that involves a direct interaction with p120RasGAP and p190RhoGAP: (i) in contrast to wt v-Fms molecules, the Y807F v-Fms protein failed to associate with and phosphorylate p120RasGAP; (ii) tight complexes between p120RasGAP and p190RhoGAP as well as detectable RhoGAP activity were present exclusively in wt-v-Fms cells; and (iii) p190RhoGAP was dispersed throughout the cytoplasm of wt-v-Fms cells, whereas its distribution was restricted to perinuclear regions of cells expressing the mutant v-Fms gene.

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Protein-tyrosine kinase (PTK, not ETK, WZC)

Springer Handbook of Enzymes

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Reassessment of the v-fms sequence: threonine phosphorylation of the COOH-terminal domain

Cited by 6 publications

References 32 publications

Isolation of new oncogenic forms of the murine c-fms gene

Isolation of new oncogenic forms of the murine c-fms gene

Tyrosine 807 of the v-Fms oncogene product controls cell morphology and association with p120RasGAP

Protein-tyrosine kinase (PTK, not ETK, WZC)

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