scholarly journals Neurotrophin-3 and FLT3 Tyrosine Kinase Receptor in Perinatal Life

2005 ◽  
Vol 2005 (1) ◽  
pp. 53-56 ◽  
Author(s):  
Ariadne Malamitsi-Puchner ◽  
Emmanouel Economou ◽  
Theodora Boutsikou ◽  
Konstantinos E. Nikolaou ◽  
Nikolaos Vrachnis
Keyword(s):  
Immune Response ◽  
Tyrosine Kinase ◽  
Nervous Tissue ◽  
Tyrosine Kinase Receptor ◽  
Term Infants ◽  
Postnatal Brain ◽  
Neonatal Life ◽  
Neurotrophin 3 ◽  
Low Levels ◽  
Circulating Levels

Our aim is to determine—in 30 healthy full-term infants and their mothers—circulating levels of neurotrophin-3 (NT-3) (important for antenatal and postnatal brain development and implicated in the immune response) and FLT3 tyrosine kinase receptor (FLT3) (controlling hematopoiesis and found in the nervous tissue), in the fetal and neonatal life. NT-3 levels, in contrast to FLT3 ones, increased significantly on the fourth postnatal day in relation to the low levels found in the mother, fetus, and day 1 neonate (P=.03, respectively). Maternal and umbilical NT3 levels positively correlated with respective FLT3 levels (P=.003andP=.03). Circulating NT-3 levels increased in early neonatal life, possibly due to exposure to various stimuli soon after birth. FLT3 levels do not seem to behave accordingly, although these two substances probably synergize.

scholarly journals TrkC Is Essential for Nephron Function and Trans-Activates Igf1R Signaling

2020 ◽  
pp. ASN.2020040424
Author(s):  
Carolin Lepa ◽  
Sascha Hoppe ◽  
Antje Stöber ◽  
Boris V. Skryabin ◽  
Laura Katharina Sievers ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Glomerular Disease ◽  
Tyrosine Kinase Receptor ◽  
Glomerular Diseases ◽  
Basement Membrane Thickening ◽  
Neurotrophin 3 ◽  
Podocyte Loss ◽  
Nephron Development ◽  
Igf1r Signaling ◽  
Igf1 Receptor

BackgroundInjury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.MethodsNephron-specific TrkC knockout (TrkC-KO) and nephron-specific TrkC-overexpressing (TrkC-OE) mice were generated to dissect the role of TrkC in nephron development and maintenance.ResultsBoth TrkC-KO and TrkC-OE mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)–associated gene expression was dysregulated in TrkC-KO mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in TrkC-OE mouse kidneys while it was decreased in TrkC-KO kidneys. Furthermore, TrkC expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.ConclusionsOur results show that TrkC is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes.

Expression of the Cell Polarity Protein PTK7 in Acute Myeloid Leukaemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1478-1478
Author(s):  
Thomas Prebet ◽  
Anne Catherine Lhoumeau ◽  
Christine Arnoulet ◽  
Sylvie Marchetto ◽  
Christian Chabannon ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cell Polarity ◽  
Molecular Mechanisms ◽  
Ectopic Expression ◽  
Leukemia Cell ◽  
Tyrosine Kinase Receptor ◽  
Low Grade ◽  
Potential Implication ◽  
Wide Range ◽  
Low Levels

Abstract The planar cell polarity pathway plays a major role in embryogenesis and tissue organisation. Recent genetic studies have highlighted the role of novel receptors and signaling molecules implicated in this pathway. Amongst the receptors, the pseudo tyrosine kinase receptor 7 (PTK7) is an orphean tyrosine kinase receptor with kinase-dead activity. Knock-out of PTK7 in mice strongly affects embryonic development leading to a major neural tube defect. Presence of PTK7 was previously investigated in epithelial and endothelial cells that both express the receptor. In normal donors, we found no expression of PTK7 in peripheral blood (n=5) whereas PTK7 expression was found with low levels in PBPC after G-CSF stimulation (n=3) and high levels in normal myeloid progenitors and CD34+ CD38− bone marrow cells (n=3). Overexpression of PTK7 was already described in solid tumors including breast, lung and pancreatic cancers. We decided to study the potential implication of PTK7 in haematological malignancies. We performed a wide range multicolour immunophenotyping screen on more than 240 patient samples treated at Institut Paoli-Calmettes and 10 leukemia cell lines. In hematologic malignancies, we demonstrated that PTK7 was widely expressed in AML (136 of 195 patients) and in the most immature subsets of Acute lymphoblastic (5 of 20 patients) or biphenotypic leukaemia (3 of 3 patients). We found no expression of PTK7 in chronic disorder such low grade NHL (n=7), CLL (n=6) or Chronic Myelomonocytic Leukemia (n=3). In AML, we demonstrated that PTK7 expression mostly correlates with granulocytic lineage differentiation and that it could be partially expressed in AML 4 or 5 subsets. Flow cytometry analysis confirmed the co-expression of PTK7 with granulocytic lineage markers and that PTK7 expression in myelomonocytic leukaemia was limited to the myeloid subset of blasts. The strongest immunophenotyping correlation was found with CD117/c-Kit expression (p<0.001) and PTK7 Mean Fluorescence Intensity directly correlates with c-Kit MFI (p=0.001). Interestingly, stimulation of cultured TF1 cells (that endogenously express c-Kit and PTK7) with SCF triggered an increased expression of PTK7. Correlation between PTK7 expression and biological or clinical features was also evaluated. We demonstrated that PTK7 expression clustered with some cytogenetic subsets (high levels in CBF AML (n=19) or APL (n=13), low levels in FLT3 mutated AML(n=17) or complex karyotype (n=20)). We also found that PTK7 expression was associated with a lower WBC count at diagnosis (p=0.001) and a lower frequency of extramedullary disease (p<0.001) in whole population and in both AML1–3 and AML 4–5 subgroups. We report here novel findings that potentially implicate ptk7, a PCP gene, in hematopoiesis and AML. In vitro, we showed that ectopic expression of PTK7 promotes cell migration, cell survival and resistance to anthracyclin-induced apoptosis. Ongoing works are currently investigating which molecular mechanisms regulate PTK7 functions in normal and pathological situations.

The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor

Cell ◽  
1991 ◽  
Vol 65 (5) ◽  
pp. 895-903 ◽  
Author(s):  
Dan Soppet ◽  
Enrique Escandon ◽  
Johnne Maragos ◽  
David S. Middlemas ◽  
Susan W. Raid ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Tyrosine Kinase Receptor ◽  
Neurotrophin 3

MEIS1 Is a Required Transcription Factor for AML Cell Proliferation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1944-1944
Author(s):  
Stefan Heinrichs ◽  
Chad J. Brenner ◽  
Rima V. Kulkarni ◽  
A. Thomas Look
Keyword(s):  
Bone Marrow ◽  
Tyrosine Kinase ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Leukemia Cell ◽  
Tyrosine Kinase Receptor ◽  
Mouse Bone Marrow ◽  
Human Leukemia ◽  
Knock Down ◽  
Low Levels

Abstract MEIS proteins constitute an important subgroup of three amino acid loop extension (TALE) class transcription factors, which are characterized by an atypical homeodomain. MEIS1 has been shown to act as an important cofactor in HOXA9-mediated leukemogenesis in bone marrow transduction experiments. In human leukemia, MEIS1 was identified as a gene consistently upregulated in leukemias with MLL translocations. However, MEIS1 overexpression is also frequently found in AMLs with normal or complex karyotypes. To investigate the role of MEIS1 in AML pathogenesis, we measured the expression of MEIS1 and MEIS2 in 26 different established human AML cell lines, and documented high levels of expression of one or both genes in 20 of these lines. Despite the prevalence of MEIS1 expression in AML blasts, the downstream pathways and their contribution to the proliferation or self-renewal of the malignant clone are not well understood. To identify gene expression programs controlled by MEIS1, we targeted MEIS1 expression by RNAi in two AML cell lines that express HOXA9 and MEIS1, but only low levels of MEIS2. In comparison to a control shRNA, cells expressing two different MEIS1-specific shRNAs were markedly deficient in thymidine incorporation indicating very low levels of cellular proliferation. The RNAi-mediated knock-down of MEIS1 expression resulted in down-regulation of the tyrosine kinase receptor FLT3 by quantitative RT-PCR. Thus our data in human AML is consistent with results of Wang et al. (Blood, 106(1):254–64) implicating MEIS1 in the regulation of FLT3 tyrosine kinase expression, based on overexpression studies in mouse bone marrow progenitors. Our results in human AML suggest that MEIS1 is required for high levels of FLT3 expression, which is significant because FLT3 is mutated and activated in these two myeloid leukemia cell lines, suggesting the hypothesis that FLT3 is an important component of the pathway through which MEIS1 promotes proliferation. Programmed re-expression of activated FLT3 in AML lines with MEIS knock-down is underway to test whether FLT3 is the essential component acting downstream of MEIS1 expression in AML pathogenesis.

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