Signal transduction via serine/threonine kinase receptors

1994 ◽  
Vol 5 (6) ◽  
pp. 389-398 ◽  
Author(s):  
Kohei Miyazono ◽  
Peter ten Dijke ◽  
Hidetoshi Yamashita ◽  
Carl-Henrik Heldin
Keyword(s):  
Signal Transduction ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

scholarly journals ROLE OF SERIN/ THREONINE KINASE INHIBITOR IN THERAPY NON-ALCOHOLIC STEATOHEPATITIS AND ALCOHOLIC HEPATITIS

2019 ◽  
Vol 6 (3) ◽  
pp. 101-109
Author(s):  
Novriantika Lestari
Keyword(s):  
Signal Transduction ◽  
Liver Fibrosis ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Binding Activity ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Receptor Binding Activity ◽  
Marked Accumulation

Liver fibrosis is a reversible response to a wound healing with marked accumulation of extracellular matrix which caused by injury to the liver. Liver fibrosis can be caused by various factors including alcohol and non-alcohol steatohepatitis. The process of fibrosis serves to localize the inflammation during chronic exposure. The hepatic stem cell (HSC) has a key role in the pathogenesis of liver fibrosis. The HSC activation is characterized by increased profibrogenic mediators including members of the TGF-? superfamily. In order to enable signal transduction, the mediator needs to bind to its receptors. The serine/ threonine kinase receptor is a receptor that binds to the TGF-? superfamily ligand, including TGF-?, BMP, activin and other mediators. The ligand receptor-binding activity will stimulate signal transduction that will translocate into the nucleus and phosphorylate various transcription factors that play a role in cell proliferation, differentiation, or apoptosis. There is currently no standard therapy for liver fibrosis. Based on the central role of the serine/ threonine kinase receptor in the pathogenesis of liver fibrosis, it is thought that the use of serine/ threonine kinase inhibitors is a promising therapy.

Mothers against dpp participates in a DDP/TGF-beta responsive serine-threonine kinase signal transduction cascade

Development ◽  
1997 ◽  
Vol 124 (16) ◽  
pp. 3167-3176 ◽  
Author(s):  
S.J. Newfeld ◽  
A. Mehra ◽  
M.A. Singer ◽  
J.L. Wrana ◽  
L. Attisano ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Nuclear Accumulation ◽  
Target Cells ◽  
Type I ◽  
Dependent Manner ◽  
Tgf Beta ◽  
Serine Threonine Kinase ◽  
Drosophila Cell ◽  
Threonine Kinase ◽  
Signal Transduction Cascade

Mothers against dpp (Mad) is the prototype of a family of genes required for signaling by TGF-beta related ligands. In Drosophila, Mad is specifically required in cells responding to Decapentaplegic (DPP) signals. We further specify the role of Mad in DPP-mediated signaling by utilizing tkvQ199D, an activated form of the DPP type I receptor serine-threonine kinase thick veins (tkv). In the embryonic midgut, tkvQ199D mimics DPP-mediated inductive interactions. Homozygous Mad mutations block signaling by tkvQ199D. Appropriate responses to signaling by tkvQ199D are restored by expression of MAD protein in DPP-target cells. Endogenous MAD is phosphorylated in a ligand-dependent manner in Drosophila cell culture. DPP overexpression in the embryonic midgut induces MAD nuclear accumulation; after withdrawal of the overexpressed DPP signal, MAD is detected only in the cytoplasm. However, in three different tissues and developmental stages actively responding to endogenous DPP, MAD protein is detected in the cytoplasm but not in the nucleus. From these observations, we discuss possible roles for MAD in a DPP-dependent serine-threonine kinase signal transduction cascade integral to the proper interpretation of DPP signals.

scholarly journals The role of Pim-2 in apoptotic signal transduction pathway of hepatocellular carcinoma

2017 ◽  
Vol 4 (4) ◽  
pp. 1380 ◽  
Author(s):  
Jiahai Chen ◽  
Xiaoli Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Signal Transduction ◽  
Mrna Expression ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Qrt Pcr

Background: Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors. The objective was to investigate the role of serine/threonine kinase Pim-2 in apoptosis signal transduction pathway, because there is little study about its contribution to apoptosis in hepatocellular carcinoma.Methods: The Pim-2 gene and protein expression were examined by qRT-PCR, Western blot and immunohistochemical stain in HCC tissues and normal liver tissues. The plasmid pCI-neo-Pim2 was transfected into human hepatoma cell line SMMC7721 by lipofectamine. Total RNAs were extracted from SMMC7721 cell in logarithm growth phase. The mRNA expression of Pim-2, Akt-1 (protein kinase B), 4E-BP1 (translation repressor of mammalian target of rapamycln), SOCS-1 (repressor of cytokine), Bad（Bcl-xL/Bcl-2 associated death promoter, Bim（Bc1-2 interacting mediator of cell death）and Puma (p53 upregulated modulator of apoptosis) were identified by qRT-PCR. The cell cycle of post-transfected SMMC7721 cells was assessed by flow cytometry.Results: Pim-2 expression was enhanced in HCC. In post-transfected SMMC7721 cells, Pim-2 mRNA expression was up-regulated, level of Bad mRNA was attenuated, furthermore, the transcription level of Akt-1, SOCS-1, 4E-BP1, Bim and Puma gene wasn’t variety. Up-graulated Pim-2 can’t cause distinct change of cell cycle or apoptosis in hepatoma cell.Conclusions: The serine/threonine kinase Pim-2 plays an import role in the development of HCC, Pim-2 dependent maintenance of cell size and survival correlated with its ability to maintain down-regulated expression of the BH3 protein Bad. Pim-2 is not a trigger in cell-autonomous survival or inhibiting apoptosis in hepatocellular carcinoma. Pim-2 is a redundancy pathway of survival signaling.

scholarly journals 14-3-3 and Erlin proteins differentially interact with RIPK2 complexes

2021 ◽  
Author(s):  
Heidrun Steinle ◽  
Kornelia Ellwanger ◽  
Nora Mirza ◽  
Selina Brise ◽  
Ioannis Kienes ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Shigella Flexneri ◽  
Biological Response ◽  
Innate Immune ◽  
Cellular Proteins ◽  
Binding Assays ◽  
Serine Threonine Kinase ◽  
Dynamic Interactions ◽  
Threonine Kinase ◽  
Innate Immune Signaling

The receptor interacting serine/threonine kinase 2 (RIPK2) is essential for signal transduction induced by the pattern-recognition receptors NOD1 and NOD2. Upon NOD1/2 activation RIPK2 forms complexes in the cytoplasm of human cells. Here, we identified the molecular composition of these complexes. Infection with Shigella flexneri to activate NOD1-RIPK2 revealed that RIPK2 formed dynamic interactions with several cellular proteins, including A20, Erlin-1, Erlin-2 and 14-3-3. Whereas interaction of RIPK2 with 14-3-3 proteins was strongly reduced upon infection with Shigella, Erlin-1 and Erlin-2 specifically bound to RIPK2 complexes. The interaction of these proteins with RIPK2 was validated by protein binding assays and immunofluorescence staining. Beside bacterial activation of NOD1/2, depletion of the E3 ligase XIAP and treatment with RIPK2 inhibitors also leads to the formation of RIPK2 cytosolic complexes. Whereas Erlin-1 and Erlin-2 were recruited to RIPK2 complexes following XIAP inhibition, they did not associate with RIPK2 structures induced by RIPK2 inhibitors. While the specific recruitment of Erlin-1/2 to RIPK2 suggests a role for these proteins in innate immune signaling, the biological response regulated by the Erlin-1/2-RIPK2 association remains to be determined.

scholarly journals PIM3 Proto-Oncogene Kinase Is a Common Transcriptional Target of Divergent EWS/ETS Oncoproteins

2003 ◽  
Vol 23 (11) ◽  
pp. 3897-3908 ◽  
Author(s):  
Benjamin Deneen ◽  
Scott M. Welford ◽  
Thu Ho ◽  
Felicia Hernandez ◽  
Irwin Kurland ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Target Genes ◽  
Lactate Production ◽  
Structural Diversity ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Genes Encoding ◽  
Signal Transduction Proteins ◽  
Nih 3T3 ◽  
Microarray Expression

ABSTRACT Despite significant structural diversity, present evidence suggests that EWS/ETS fusion proteins promote oncogenesis by transcriptionally modulating a common set of target genes. In order to identify these genes, microarray expression analyses were performed on NIH 3T3 polyclonal populations expressing one of three EWS/ETS fusion genes. The majority of these genes can be grouped into seven functional categories, including cellular metabolism and signal transduction. The biologic significance of these target genes was pursued. The effects of modulating genes involved in metabolism were assessed by flux studies and demonstrated shifts in glucose utilization and lactate production as a result of EWS/FLI1 expression. The proto-oncogene coding for serine/threonine kinase PIM3 was found to one of several genes encoding signal transduction proteins that were up-regulated by EWS/ETS fusions. PIM3 was found to be expressed in a panel of human Ewing's family tumor cell lines. Forced expression of PIM3 promoted anchorage-independent growth. Coexpression of a kinase-deficient PIM3 mutant attenuated EWS/FLI1-mediated NIH 3T3 tumorigenesis in immunodeficent mice.

Signal Transduction by Serine/Threonine Kinase-Coupled Receptors

2017 ◽  
pp. 229-247
Author(s):  
Friedrich Marks ◽  
Ursula Klingmüller ◽  
Karin Müller-Decker
Keyword(s):  
Signal Transduction ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

Abstract 204: Serine Threonine Kinase-35 Regulates Diabetes-induced Endothelial Progenitor Cells Dysfunction

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Darukeshwara Joladarashi ◽  
Rajarajan A. Thandavarayan ◽  
Sahana Suresh Babu ◽  
Prince Jeyabal ◽  
Raj Kishore ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Progenitor Cells ◽  
Protein Kinases ◽  
Endothelial Progenitor Cells ◽  
High Glucose ◽  
Diabetic Mice ◽  
Serine Threonine Kinase ◽  
Endothelial Progenitor ◽  
Threonine Kinase

The completion of the sequencing of the human genome has revealed that up to ~20% of the human genes encode proteins involved in signal transduction. Among these, there are >500 protein kinases. Protein kinases play a central role in the intracellular signal transduction systems involved in cell proliferation, differentiation, metabolism, and other responses to external stimuli. Serine Threonine Kinase 35 (STK35), a novel kinase that binds to nuclear actin, has been shown to regulate important cellular functions such as cell migration, proliferation, survival, and angiogenesis. However, the role of STK35 in Endothelial Progenitor Cells (EPC) function and in cardiac regeneration under diabetic condition is unknown. The purpose of this study was to determine the role of STK35 in diabetes-induced EPC dysfunction. The expression of STK35 in response to high glucose was measured by RT-PCR. STK35 expression was assessed in myocardial tissue from both human patients and mice with diabetes. To enable detailed study of STK35 biological effects in EPCs, we performed loss-of-function experiments by STK35 inhibition in EPCs. EPC from bone marrow of mice and exposed to high glucose level, showed decreased STK35 expression (vs normoglycemia-treated cells). In addition, STK35 knockdown in EPCs reduces their migration and vascular tube formation. Moreover, STK35 knockdown in EPCs have shown decreased in the expression of proangiogenic cytokines and growth factors. Results from both diabetic human heart and diabetic mice heart have also shown lower STK35 expression as compared to respective non-diabetic hearts. Taken together, these data suggest that diabetes decreases STK35 expression in EPCc thereby impairs EPC function under diabetic condition. Our future studies will test whether ex-vivo STK35-overexpression in EPCs rescues diabetes-induced dysfunction and whether their transplantation into myocardium of diabetic mice promotes angiogenesis and cardiac repair after injury.

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