Growth of factor-dependent hemopoietic precursor cell lines.

Dexter, T. M.; Garland, John M.; Scott, D; Scolnick, Edward M.; Metcalf, Donald

doi:10.1084/jem.152.4.1036

Cited by 729 publications

(300 citation statements)

References 16 publications

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“…IL-3 independent survival of progenitor cells harboring HPK1-N. To further analyze the role of the HPK1 cleavage fragments, we took advantage of the mouse myeloid progenitor cell line FDC-P1 16 and using retroviral transduction generated cell clones stably expressing either HPK1-N or HPK1-C (Figure 2a). Five clones (N-1 to N-5 and C-1 to C-5, respectively) were pooled for subsequent analysis to avoid effects of clonal variation and compared to pooled clones containing the virus without insert (vector).…”

Section: Resultsmentioning

confidence: 99%

“…Suspension cells were harvested, IL-3 was removed from the cell culture medium and cells were differentiated for an additional 7 days in cell culture medium supplemented with M-CSF. Primary mouse progenitor cells and the IL-3 dependent mouse hematopoietic progenitor cell line FDC-P1 16 were cultured in Dulbecco's modified Eagle's medium (Life Technologies) supplemented with 5% fetal bovine serum (Sigma), 100 mg/ml penicillin (Life Technologies), 100 mg/ml streptomycin (Life Technologies), 20 mM L-glutamine (Life Technologies), 0.001% monothioglycerol (Sigma) and 1.5% conditioned medium of the myeloma cell line X63 Ag8-653 IL-3 as a source of IL-3. 17 During culture of primary mouse progenitor cells, 10% conditioned medium of the cell line L929 was added as a source of M-CSF.…”

Section: Methodsmentioning

confidence: 99%

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Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation

et al. 2006

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We studied monocytic differentiation of primary mouse progenitor cells to understand molecular mechanisms of differentiation. We found a tightly controlled non-apoptotic activation of caspase-3 that correlated with differentiation. Although caspase activity was already detected during monocytic differentiation, a caspase-3 target has not been identified yet. We show that hematopoietic progenitor kinase 1 (HPK1) is processed towards its N-and C-terminal fragments during monocytic differentiation. While HPK1 is an immunoreceptor-proximal kinase in T and B cells, its role in myeloid cells is elusive. Here, we show that the N-terminal cleavage product, HPK1-N, comprising the kinase domain, confers progenitor cell survival independent of the growth factor IL-3. Furthermore, HPK1-N causes differentiation of progenitor cells towards the monocytic lineage. In contrast to full-length kinase, HPK1-N is constitutively active causing sustained JNK activation, Bad phosphorylation and survival. Blocking of caspase activity during differentiation of primary mouse progenitor cells leads to reduced HPK1-N levels, suppressed JNK activity and attenuated monocytic differentiation. Our work explains growth factor-independent survival during monocytic differentiation by caspase-mediated processing of HPK1 towards HPK1-N. Cell Death and Differentiation (2007) 14, 568-575. doi:10.1038/sj.cdd.4402042; published online 6 October 2006Within the hematopoietic system lineage commitment, differentiation and proliferation are precisely balanced throughout life, resulting in adjusted levels of myeloid and lymphoid cells. A complicated network of cytokines essentially contributes to hematopoietic homeostasis. Myeloid progenitor cells and myeloid-like cell lines respond to the cytokine interleukine-3 (IL-3) with proliferation and survival. 1 While removal of IL-3 results in cell death via apoptosis, suppression of apoptosis allows differentiation of the mouse hematopoietic progenitor cell line FDC-P1 in the absence of IL-3. 2 Monocytic differentiation of primary bone marrow and fetal liver progenitors or myeloid cell lines can be induced by IL-3 withdrawal and stimulation with monocyte-colony stimulating factor (M-CSF). 3 Monocytic differentiation is accompanied by caspase activation; 4,5 however, the molecular targets of caspase activity during monocytic differentiation have not been identified.Hematopoietic progenitor kinase 1 (HPK1) is comprised of a catalytic domain with extensive homology to the Sterile 20 kinase of the yeast Saccharomyces cerevisiae and a Cterminally located regulatory domain, called citron homology domain. 6 Ectopic expression renders full-length HPK1 active in epithelial cells resulting in selective activation of the JNK and the NFkB pathways. 7,8 Upon caspase-3 cleavage the N-terminal kinase domain of HPK1 (HPK1-N) is separated from the C-terminus (HPK1-C) resulting in suppression of NFkB. 8 In non-stimulated lymphocytes, HPK1 kinase activity is hardly detectable, but antigen receptor crosslinking leads to profound HPK1...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation

et al. 2006

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“…The recent molecular cloning of murine IL3 [5] together with the establishment of IL3-dependent cell lines [6] has allowed investigations into the biochemical mechanisms of IL3 actions. In previous reports we described the IL3-dependent translocation of PK-C as well as the serine/threonine phosphorylation of several proteins that were also phosphorylated in response to pharmacological activators of PK-C [I-3].…”

Section: Introductionmentioning

confidence: 99%

Interleukin 3 and phorbol ester stimulate tyrosine phosphorylation of overlapping substrate proteins

Ferris

Willette-Brown

Martensen³

et al. 1989

FEBS Letters

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FDC-PI is a murine myeloid cell line that requires interleukin 3 (IL3) for survival and proliferation. While the biological effects of IL3 have been well described, the biochemical mechanisms of IL3 actions have only recently been examined. We have investigated whether IL3 or PMA stimulates phosphorylation of proteins on tyrosine as well as on serine/threonine residues as previously described [(1986) Blood 68, 906-913; (1987) Biochem. J. 244, 683-691]. Here we report that both IL3 and PMA stimulate the tyrosine phosphorylation of at least two proteins: pp70 and pp50 in FDC-P1 cells.

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“…13,59,61,62,66 The murine IAPLTRs (LS-IAP-LTR, PCI-IAP-LTR, and PCII-IAP-LTR), the MoMuLV-LTR, and the human HTLV-I, HTLV-II, HIV retroviral…”

Section: Nuclear Run-on Transcription Assaysmentioning

confidence: 99%

“…[42][43][44][45] HTLV-II was origpSV2neo expression vector as described ( Figure 1). 61 To faciliinally isolated from patients with hairy cell leukemia. 46,47 tate further manipulations, a 5′ end unique EcoRI site was cre-HTLV-II is closely related to HTLV-I, and also encodes a tax ated which resulted in p5′EcoRI-gIL3.…”

mentioning

confidence: 99%

Differential effects of retroviral long terminal repeats on interleukin-3 gene expression and autocrine transformation

McCubrey

1997

Leukemia

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Growth of factor-dependent hemopoietic precursor cell lines.

Cited by 729 publications

References 16 publications

Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation

Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation

Interleukin 3 and phorbol ester stimulate tyrosine phosphorylation of overlapping substrate proteins

Differential effects of retroviral long terminal repeats on interleukin-3 gene expression and autocrine transformation

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