G alpha(i-2) mediates renal LLC-PK1 growth by a Raf-independent activation of p42/p44 MAP kinase

1997 ◽  
Vol 272 (2) ◽  
pp. F273-F282 ◽  
Author(s):  
T. B. Kinane ◽  
I. Kang ◽  
A. Chu ◽  
S. H. Chin ◽  
L. Ercolani
Keyword(s):  
Cell Growth ◽  
Protein Kinases ◽  
Doubling Time ◽  
Active Form ◽  
Renal Cells ◽  
Downstream Effectors ◽  
Mitogen Activated Protein ◽  
Cell Doubling Time ◽  
Cell Growth And Differentiation ◽  
Maximal Expression

The protooncogene G alpha(i-2) plays a pivotal role in signaling pathways that control renal cell growth and differentiation. Mitogen-activated protein kinases (MAPKs) are potential downstream effectors for G alpha(i-2) in these pathways. In predifferentiated LLC-PK1 renal cells, the temporal maximal expression of G alpha(i-2) coincided with maximal activation of MAPK(p42/p44). By contrast, pertussis toxin treatment of these cells inhibited cell growth and reduced MAPK(p42/p44) activity by 30%. These findings reflected upstream activation of MAPK kinase (MEK1), as transient transfection of cells with a plasmid encoding a constitutively active form of MEK1 increased MAPK(p42/p44) activity and cell growth, whereas treatment with PD-098059, an inhibitor of MEK1 activity, reduced MAPK(p42/p44) activity and cell growth. Expression of a guanosinetriphosphatase (GTPase)-deficient G alpha(i-2) in these cells increased MAPK(p42/p44) activity and correspondingly reduced cell doubling time from 24 to 10 h without altering the activity of Raf-1 or c-Jun/stress-activated protein kinases (SAPKs). By contrast, expression of a GTPase-deficient G alpha(i-3) in these cells reduced both their cell doubling time by 30% and MAPK(p42/p44) activity by 60%. As the known MEKK isoforms (MEKK1, -2, and -3) can also activate SAPKs, these findings suggest the GTP-charged G alpha(i-2) subunit transduces growth signals in renal cells via activation of MAPK(p42/p44) and that such activation may be linked to pathways containing novel MEKK isoforms that preferentially activate MEKs.

scholarly journals Modelling of active forms of protein kinases: p38--a case study.

1997 ◽  
Vol 44 (3) ◽  
pp. 557-564
Author(s):  
K Ginalski ◽  
B Lesyng ◽  
J Sowadski ◽  
M Wojciechowski
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
General Scheme ◽  
Active Form ◽  
Binding Mode ◽  
Extracellular Signal Regulated Kinase ◽  
Inactive Form ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

An active form of p38 protein kinase, belonging to the mitogen-activated protein kinases subfamily, has been designed based on crystallographically known structures of two other kinases, an active form of protein kinase A (PKA) and an inactive form of extracellular signal-regulated kinase 2 (ERK2). The modelling procedure is described. Its general scheme can also be applied to other kinases. The structure of the active forms of p38 and PKA is very similar in the region which binds the substrate. The ATP-binding mode is very similar in the active forms of all the three studied kinases. Models of the active forms allow for further studies on transphosphorylation processes at the molecular level, and modelling of inhibitors competitive with ATP and/or substrates.

scholarly journals Expression and activity of mitogen activated protein kinases in human colorectal carcinoma

Gut ◽  
1999 ◽  
Vol 44 (6) ◽  
pp. 834-838 ◽  
Author(s):  
S Eggstein ◽  
M Franke ◽  
I Kutschka ◽  
G Manthey ◽  
B U von Specht ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Normal Mucosa ◽  
Mitogen Activated Protein Kinases ◽  
Colorectal Mucosa ◽  
Mapk Activity ◽  
Mitogen Activated Protein ◽  
Colonic Carcinogenesis ◽  
Cell Growth And Differentiation ◽  
Expression And Activity

BACKGROUNDMitogen activated protein kinases (MAPKs) play a central role in the regulation of both cell growth and differentiation. They are involved in signal transduction of oncogenes and growth factors. The role of MAPK in colonic carcinoma is unknown.AIMSTo establish whether the expression and activity of p42/44 MAPKs are altered in colorectal tumours as compared with normal mucosa.METHODSThe expression and activity of p42/p44 MAPK were investigated in 22 colorectal carcinomas, four adenomas, and the corresponding normal colorectal mucosa by the use of western blotting, immunoprecipitation, and in vitro kinase assays.RESULTSAfter immunoprecipitation with an antibody specific for p42 MAPK, we found significant inactivation of p42 MAPK in colonic carcinomas as well as in adenomas, whereas most sample pairs showed only minor differences in p42 MAPK expression. Investigation of MAPK with an antibody capable of detecting both p42 and p44 MAPK showed a slight but significant decrease in p44 MAPK content in malignant tissues. With this antibody, only minor alterations in MAPK activity and no correlation with p42 MAPK activity were found.CONCLUSIONSInactivation of p42 MAPK could be associated with colonic carcinogenesis.

scholarly journals Elimination of [PSI+] Prion and Influence on Yeast Cell Growth

2022 ◽  
Author(s):  
Justina Versockienė ◽  
Neda Jonutytė-Trembo ◽  
Vitalij Novickij ◽  
Eglė Lastauskienė
Keyword(s):  
Cell Growth ◽  
Optical Density ◽  
Doubling Time ◽  
Prion Proteins ◽  
Growth Dynamics ◽  
Model System ◽  
Cell Doubling Time ◽  
Culture Growth ◽  
Positive Effect

Abstract Background Prions are proteinaceous infectious particles that act as pathogens and cause the development of lethal neurodegenerative diseases in humans and other animals. Yeast Saccharomyces cerevisiae is a widespread model system in which mechanisms of prion induction and elimination have been identified. New and safe substances and methods are being sought to cure cells of prion proteins. It is particularly important that by treating cells from prions and restoring them from the [PSI+] to the [psi−] form, the primary growth of the cells is restored. One of the main objectives of this study was to determine the growth dynamics of S. cerevisiae cells with different [PSI+] prion variants, cells that have lost [PSI+] prion variants, and cells that never had [PSI+] prion variants. Results In this research, we applied GuHCl and combined GuHCl and PEF treatment against [PSI+] prion. We evaluated cells culture growth dynamics – optical density and doubling time and determined that method of [PSI+] prion elimination does not affect cell doubling time. Also, we found that both elimination methods affect the optical density reached by [psi−] cells. However, the cells in which the [PSI+] prion has been eliminated by GuHCl alone are able to reach the same optical density as unaffected [psi−] cells and higher optical density than the affected [psi−] cells by GuHCl alone. Conclusions These findings indicate the potential long-term positive effect of [PSI+] prion on cell growth, which persists after [PSI+] removal.

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