Regulation of Hepatic Glucose Production by Transforming Growth Factor Beta 1 via Protein Kinase A

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2441-PUB ◽  
Author(s):  
QUAN PAN ◽  
YUNMEI CHEN ◽  
HUI YAN ◽  
WANBAO YANG ◽  
ZHENG SHEN ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose ◽  
Growth Factor Beta ◽  
Kinase A

Transforming growth factor-beta inhibits phosphate transport in renal epithelial cells

1993 ◽  
Vol 264 (4) ◽  
pp. F623-F628 ◽  
Author(s):  
F. Law ◽  
R. Rizzoli ◽  
J. P. Bonjour
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Renal Epithelial Cells ◽  
Pi Transport ◽  
Sodium Dependent ◽  
Growth Factor Beta

The effect(s) of transforming growth factor-beta (TGF-beta) on Pi transport was investigated in confluent opossum kidney (OK) epithelial cells. TGF-beta induced a time- and concentration-dependent decrease in the initial rate of sodium-dependent Pi, but not alanine, transport. This selective inhibitory effect on Pi transport was largely reversible and was not associated with a rise in adenosine 3',5'-cyclic monophosphate production. The reduction in Pi uptake was also independent of changes in extracellular calcium concentrations and prostaglandin synthesis. TGF-beta-mediated Pi transport inhibition appeared to involve neither pertussis toxin-sensitive G protein(s) nor augmented protein kinase C activity. However, the probable role of a serine/threonine protein kinase in signal transduction was supported by the considerable attenuation of TGF-beta effect by H-7. Furthermore, the TGF-beta-induced Pi transport reduction was blunted by cycloheximide and abolished by actinomycin D. In conclusion, TGF-beta selectively inhibits the activity of the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. This action appears to be exerted via an unprecedented inhibitory pathway that might involve a serine/threonine protein kinase and alterations in the transcriptional and translational processes.

scholarly journals Protein Kinase A Modulates Transforming Growth Factor-β Signaling through a Direct Interaction with Smad4 Protein

2013 ◽  
Vol 288 (12) ◽  
pp. 8737-8749 ◽  
Author(s):  
Huibin Yang ◽  
Gangyong Li ◽  
Jing-Jiang Wu ◽  
Lidong Wang ◽  
Michael Uhler ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Transforming Growth Factor ◽  
Direct Interaction ◽  
Transforming Growth Factor Β ◽  
Smad4 Protein ◽  
Kinase A

scholarly journals Evidence for the involvement of protein kinase activity in transforming growth factor-beta signal transduction.

1992 ◽  
Vol 12 (1) ◽  
pp. 261-265 ◽  
Author(s):  
M Ohtsuki ◽  
J Massagué
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
G1 Phase ◽  
Tgf Beta ◽  
Kinase C ◽  
Growth Factor Beta ◽  
Pai 1

Transforming growth factor-beta 1 (TGF-beta 1) rapidly increases the expression of junB transcription factor and plasminogen activator inhibitor-1 (PAI-1) and prevents the cell cycle-dependent phosphorylation of the RB retinoblastoma susceptibility gene product during late G1 phase in Mv1Lu lung epithelial cells. These responses are shown in this report to be blocked by the potent serine/threonine protein kinase inhibitor, H7, added with TGF-beta 1. Added alone, H7 does not alter the basal junB or PAI-1 mRNA levels, the deposition of PAI-1 into the extracellular matrix, or the phosphorylation of RB in late G1 phase, suggesting that this inhibitor does not have a general nonspecific effect on the cell. The analogs H8 and H9, which are preferential inhibitors of cyclic nucleotide-dependent protein kinases, are fivefold less potent than H7 as inhibitors of the TGF-beta response. The PAI-1 response to TGF-beta 1 is not affected by the simultaneous addition of staurosporine, which is a protein kinase C inhibitor, or by the prolonged preincubation of cells with phorbol 12-myristate 13-acetate, which down-regulates protein kinase C. The results suggest the possibility that H7 and its analogs block various early TGF-beta responses by inhibiting a protein serine/threonine kinase(s).

Evidence for the involvement of protein kinase activity in transforming growth factor-beta signal transduction

1992 ◽  
Vol 12 (1) ◽  
pp. 261-265
Author(s):  
M Ohtsuki ◽  
J Massagué
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
G1 Phase ◽  
Tgf Beta ◽  
Kinase C ◽  
Growth Factor Beta ◽  
Pai 1

Transforming growth factor-beta 1 (TGF-beta 1) rapidly increases the expression of junB transcription factor and plasminogen activator inhibitor-1 (PAI-1) and prevents the cell cycle-dependent phosphorylation of the RB retinoblastoma susceptibility gene product during late G1 phase in Mv1Lu lung epithelial cells. These responses are shown in this report to be blocked by the potent serine/threonine protein kinase inhibitor, H7, added with TGF-beta 1. Added alone, H7 does not alter the basal junB or PAI-1 mRNA levels, the deposition of PAI-1 into the extracellular matrix, or the phosphorylation of RB in late G1 phase, suggesting that this inhibitor does not have a general nonspecific effect on the cell. The analogs H8 and H9, which are preferential inhibitors of cyclic nucleotide-dependent protein kinases, are fivefold less potent than H7 as inhibitors of the TGF-beta response. The PAI-1 response to TGF-beta 1 is not affected by the simultaneous addition of staurosporine, which is a protein kinase C inhibitor, or by the prolonged preincubation of cells with phorbol 12-myristate 13-acetate, which down-regulates protein kinase C. The results suggest the possibility that H7 and its analogs block various early TGF-beta responses by inhibiting a protein serine/threonine kinase(s).

scholarly journals A Transforming Growth Factor β-Induced Smad3/Smad4 Complex Directly Activates Protein Kinase A

2004 ◽  
Vol 24 (5) ◽  
pp. 2169-2180 ◽  
Author(s):  
Lizhi Zhang ◽  
Chao Jun Duan ◽  
Charles Binkley ◽  
Gangyong Li ◽  
Michael D. Uhler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Transforming Growth Factor ◽  
Direct Interaction ◽  
Transforming Growth Factor Β ◽  
Regulatory Subunit ◽  
Smad Proteins ◽  
Kinase A

ABSTRACT Transforming growth factor β (TGFβ) interacts with cell surface receptors to initiate a signaling cascade critical in regulating growth, differentiation, and development of many cell types. TGFβ signaling involves activation of Smad proteins which directly regulate target gene expression. Here we show that Smad proteins also regulate gene expression by using a previously unrecognized pathway involving direct interaction with protein kinase A (PKA). PKA has numerous effects on growth, differentiation, and apoptosis, and activation of PKA is generally initiated by increased cellular cyclic AMP (cAMP). However, we found that TGFβ activates PKA independent of increased cAMP, and our observations support the conclusion that there is formation of a complex between Smad proteins and the regulatory subunit of PKA, with release of the catalytic subunit from the PKA holoenzyme. We also found that the activation of PKA was required for TGFβ activation of CREB, induction of p21Cip1, and inhibition of cell growth. Taken together, these data indicate an important and previously unrecognized interaction between the TGFβ and PKA signaling pathways.

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