RGS16 is a negative regulator of SDF-1–CXCR4 signaling in megakaryocytes

Blood ◽  
2005 ◽  
Vol 106 (9) ◽  
pp. 2962-2968 ◽  
Author(s):  
Magali Berthebaud ◽  
Christel Rivière ◽  
Peggy Jarrier ◽  
Adlen Foudi ◽  
Yanyan Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
G Protein ◽  
Receptor Expression ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Rgs Proteins ◽  
Cxcr4 Signaling ◽  
Chemokine Signaling ◽  
Mitogen Activated Protein ◽  
Stromal Cell Derived Factor

AbstractRegulators of G-protein signaling (RGS) constitute a family of proteins involved in the negative regulation of signaling through heterotrimeric G protein–coupled receptors (GPCRs). Several RGS proteins have been implicated in the down-regulation of chemokine signaling in hematopoietic cells. The chemokine stromal-cell–derived factor 1 (SDF-1) activates migration of hematopoietic progenitors cells but fails to activate mature megakaryocytes despite high levels of CXC chemokine receptor 4 (CXCR4) receptor expression in these cells. This prompted us to analyze RGS expression and function during megakaryocyte differentiation. We found that RGS16 and RGS18 mRNA expression was up-regulated during this process. Overexpressing RGS16 mRNA in the megakaryocytic MO7e cell line inhibited SDF-1–induced migration, mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) activation, whereas RGS18 overexpression had no effect on CXCR4 signaling. Knocking down RGS16 mRNA via lentiviral-mediated RNA interference increased CXCR4 signaling in MO7e cells and in primary megakaryocytes. Thus, our data reveal that RGS16 is a negative regulator of CXCR4 signaling in megakaryocytes. We postulate that RGS16 regulation is a mechanism that controls megakaryocyte maturation by regulating signals from the microenvironment.

scholarly journals Two human cDNAs, including a homolog of Arabidopsis FUS6 (COP11), suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction in yeast and mammalian cells.

1996 ◽  
Vol 16 (12) ◽  
pp. 6698-6706 ◽  
Author(s):  
B H Spain ◽  
K S Bowdish ◽  
A R Pacal ◽  
S F Staub ◽  
D Koo ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
G Protein ◽  
Mammalian Cells ◽  
Enhanced Recovery ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Striking Similarity ◽  
Protein Subunit ◽  
Mitogen Activated Protein

We have isolated two novel human cDNAs, gps1-1 and gps2, that suppress lethal G-protein subunit-activating mutations in the pheromone response pathway of the yeast Saccharomyces cerevisiae. Suppression of other pathway-activating events was examined. In wild-type cells, expression of either gps1-1 or gps2 led to enhanced recovery from cell cycle arrest induced by pheromone. Sequence analysis indicated that gps1-1 contains only the carboxy-terminal half of the gps1 coding sequence. The predicted gene product of gps1 has striking similarity to the protein encoded by the Arabidopsis FUS6 (COP11) gene, a negative regulator of light-mediated signal transduction that is known to be essential for normal development. A chimeric construct containing gps1 and FUS6 sequences also suppressed the yeast pheromone pathway, indicating functional conservation between these human and plant genes. In addition, when overexpressed in mammalian cells, gps1 or gps2 potently suppressed a RAS- and mitogen-activated protein kinase-mediated signal and interfered with JNK activity, suggesting that signal repression is part of their normal function. For gps1, these results are consistent with the proposed function of FUS6 (COP11) as a signal transduction repressor in plants.

Protein kinase A acts at multiple points to inhibit Xenopus oocyte maturation

1994 ◽  
Vol 14 (7) ◽  
pp. 4419-4426
Author(s):  
W Matten ◽  
I Daar ◽  
G F Vande Woude
Keyword(s):  
Protein Kinase ◽  
Xenopus Oocytes ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Mobility Shift ◽  
Dependent Protein Kinase ◽  
Multiple Points ◽  
Mitogen Activated Protein ◽  
Dependent Protein ◽  
Phosphatase Activation

In Xenopus oocytes, initiation of maturation is dependent on reduction of cyclic AMP-dependent protein kinase (PKA) activity and the synthesis of the mos proto-oncogene product. Mos is required during meiosis I for the activation of both maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK). Here we show that injection of the catalytic subunit of PKA (PKAc) prevented progesterone-induced synthesis of endogenous Mos as well as downstream MPF and MAPK activation. However, PKAc did not prevent injected soluble Mos product from activating MAPK. While MAPK is activated during Mos-PKAc coinjection, attendant MPF activation is blocked. Additionally, PKAc caused a potent block in the electrophoretic mobility shift of cdc25 that is associated with phosphatase activation. This inhibition of cdc25 activity was not reversed by progesterone, Mos, or MPF. We conclude that PKAc acts as a negative regulator at several points in meiotic maturation by preventing both Mos translation and MPF activation.

scholarly journals The Same Receptor, G Protein, and Mitogen-activated Protein Kinase Pathway Activate Different Downstream Regulators in the Alternative White and Opaque Pheromone Responses ofCandida albicans

2008 ◽  
Vol 19 (3) ◽  
pp. 957-970 ◽  
Author(s):  
Song Yi ◽  
Nidhi Sahni ◽  
Karla J. Daniels ◽  
Claude Pujol ◽  
Thyagarajan Srikantha ◽  
...  
Keyword(s):  
Protein Kinase ◽  
G Protein ◽  
Basal Layer ◽  
Mitogen Activated Protein Kinase ◽  
Expression Of Genes ◽  
Ofcandida Albicans ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Alternative Responses

Candida albicans must undergo a switch from white to opaque to mate. Opaque cells then release mating type-specific pheromones that induce mating responses in opaque cells. Uniquely in C. albicans, the same pheromones induce mating-incompetent white cells to become cohesive, form an adhesive basal layer of cells on a surface, and then generate a thicker biofilm that, in vitro, facilitates mating between minority opaque cells. Through mutant analysis, it is demonstrated that the pathways regulating the white and opaque cell responses to the same pheromone share the same upstream components, including receptors, heterotrimeric G protein, and mitogen-activated protein kinase cascade, but they use different downstream transcription factors that regulate the expression of genes specific to the alternative responses. This configuration, although common in higher, multicellular systems, is not common in fungi, and it has not been reported in Saccharomyces cerevisiae. The implications in the evolution of multicellularity in higher eukaryotes are discussed.

scholarly journals Stress-induced Protein Phosphatase 2C Is a Negative Regulator of a Mitogen-activated Protein Kinase

2003 ◽  
Vol 278 (21) ◽  
pp. 18945-18952 ◽  
Author(s):  
Irute Meskiene ◽  
Emmanuel Baudouin ◽  
Alois Schweighofer ◽  
Aneta Liwosz ◽  
Claudia Jonak ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Phosphatase ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Protein Phosphatase 2C ◽  
Mitogen Activated Protein
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