A dual role for the protein kinase shaggy in the repression of achaete­scute

Development ◽  
1993 ◽  
Vol 119 (Supplement) ◽  
pp. 29-39 ◽  
Author(s):  
Pat Simpson ◽  
Laurent Ruel ◽  
Pascal Heitzler ◽  
Marc Bourouis
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Glycogen Synthase ◽  
Precursor Cell ◽  
The Other ◽  
Glycogen Synthase Kinase 3 ◽  
Neural Precursor ◽  
Constitutive Activity ◽  
Molecular Studies ◽  
Restricted Pattern

achaete and scute are expressed in a spatially restricted pattern and provide neural potential to cells. The domains of expression depend partly on extramacrochaetae whose product is itself spatially restricted and acts as a negative post-translational regulator of achaete and scute. The protein kinase shaggy also represses achaete and scute at many sites but may act via intermediate transcription factors. However shaggy and exlramacrochaetae act synergistically and molecular studies suggest that they may be part of the same pathway, shaggy is functionally homologous to the mammalian glycogen synthase kinase-3 and analogy with the known physiology of this enzyme, suggests that this function of shaggy may result from the “constitutive” activity. At the site where a single neural precursor will develop, achaete and scute are initially expressed in a group of equivalent cells. The genes Notch and Delta are part of a lateral signal required to single out one precursor cell and to silence achaete and scute expression in the other cells, shaggy is required downstream of Notch for transduction of the inhibitory signal. This second role or shaggy may be due to modulation or enzymatic activity during signalling.

scholarly journals TcR and TcR-CD28 Engagement of Protein Kinase B (PKB/AKT) and Glycogen Synthase Kinase-3 (GSK-3) Operates Independently of Guanine Nucleotide Exchange Factor VAV-1

2006 ◽  
Vol 281 (43) ◽  
pp. 32385-32394 ◽  
Author(s):  
Joanne E. Wood ◽  
Helga Schneider ◽  
Christopher E. Rudd
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
Glycogen Synthase ◽  
Protein Kinase B ◽  
Guanine Nucleotide Exchange Factor ◽  
Glycogen Synthase Kinase 3 ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor

TcRζ/CD3 and TcRζ/CD3-CD28 signaling requires the guanine nucleotide exchange factor (GEF) Vav-1 as well as the activation of phosphatidylinositol 3-kinase, protein kinase B (PKB/AKT), and its inactivation of glycogen synthase kinase-3 (GSK-3). Whether these two pathways are connected or operate independently of each other in T-cells has been unclear. Here, we report that anti-CD3 and anti-CD3/CD28 can induce PKB and GSK-3α phosphorylation in the Vav-1–/– Jurkat cell line J. Vav.1 and in primary CD4-positive Vav-1–/– T-cells. Reduced GSK-3α phosphorylation was observed in Vav-1,2,3–/– T-cells together with a complete loss of FOXO1 phosphorylation. Furthermore, PKB and GSK-3 phosphorylation was unperturbed in the presence of GEF-inactive Vav-1 that inhibited interleukin-2 gene activation and a form of Src homology 2 domain-containing lymphocytic protein of 76-kDa (SLP-76) that is defective in binding to Vav-1. The pathway also was intact under conditions of c-Jun N-terminal kinase (JNK) inhibition and disruption of the actin cytoskeleton by cytochalasin D. Both events are down-stream targets of Vav-1. Overall, our findings indicate that the TcR and TcR-CD28 driven PKB-GSK-3 pathway can operate independently of Vav-1 in T-cells.

Analysis of RIM11, a yeast protein kinase that phosphorylates the meiotic activator IME1

1994 ◽  
Vol 14 (12) ◽  
pp. 7909-7919 ◽  
Author(s):  
K S Bowdish ◽  
H E Yuan ◽  
A P Mitchell
Keyword(s):  
Protein Kinase ◽  
Immune Complexes ◽  
Functional Relationship ◽  
Biological Function ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Yeast Protein ◽  
Yeast Genes

Many yeast genes that are essential for meiosis are expressed only in meiotic cells. Known regulators of early meiotic genes include IME1, which is required for their expression, and SIN3 and UME6, which prevent their expression in nonmeiotic cells. We report here the molecular characterization of the RIM11 gene, which we find is required for expression of several early meiotic genes. A close functional relationship between RIM11 and IME1 is supported by two observations. First, sin3 and ume6 mutations are epistatic to rim11 mutations; prior studies have demonstrated their epistasis to ime1 mutations. Second, overexpression of RIM11 can suppress an ime1 missense mutation (ime1-L321F) but not an ime1 deletion. Sequence analysis indicates that RIM11 specifies a protein kinase related to rat glycogen synthase kinase 3 and the Drosophila shaggy/zw3 gene product. Three partially defective rim11 mutations alter residues involved in ATP binding or catalysis, and a completely defective rim11 mutation alters a tyrosine residue that corresponds to the site of an essential phosphorylation for glycogen synthase kinase 3. Immune complexes containing a hemagglutinin (HA) epitope-tagged RIM11 derivative, HA-RIM11, phosphorylate two proteins, p58 and p60, whose biological function is undetermined. In addition, HA-RIM11 immune complexes phosphorylate a functional IME1 derivative but not the corresponding ime1-L321F derivative. We propose that RIM11 stimulates meiotic gene expression through phosphorylation of IME1.

scholarly journals Multiple mechanisms for the phosphorylation of C-terminal regulatory sites in rabbit muscle glycogen synthase expressed in COS cells

1996 ◽  
Vol 313 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Alexander V. SKURAT ◽  
Peter J. ROACH
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Rabbit Muscle ◽  
Cos Cells ◽  
Additional Mutation ◽  
Regulatory Sites

Glycogen synthase can be inactivated by sequential phosphorylation at the C-terminal residues Ser652 (site 4), Ser648 (site 3c), Ser644 (site 3b) and Ser640 (site 3a) catalysed by glycogen synthase kinase-3. In vitro, glycogen synthase kinase-3 action requires that glycogen synthase has first been phosphorylated at Ser656 (site 5) by casein kinase II. Recently we demonstrated that inactivation is linked only to phosphorylation at site 3a and site 3b, and that, in COS cells, modification of these sites can occur by alternative mechanisms independent of any C-terminal phosphorylations [Skurat and Roach (1995) J. Biol. Chem. 270, 12491-12497]. To address these mechanisms multiple Ser → Ala mutations were introduced in glycogen synthase such that only site 3a or site 3b remained intact. Additional mutation of Arg637 → Gln eliminated phosphorylation of site 3a, indicating that Arg637 may be important for recognition of site 3a by its corresponding protein kinase(s). Similarly, additional mutation of Pro645 → Ala eliminated phosphorylation of site 3b, indicating a possible involvement of ‘proline-directed’ protein kinase(s). Mutation of Arg637 alone did not activate glycogen synthase as expected from the loss of phosphorylation at site 3a. Rather, mutation of both Arg637 and the Ser → Ala substitution at site 3b was required for substantial activation. The results suggest that sites 3a and 3b can be phosphorylated independently of one another by distinct protein kinases. However, phosphorylation of site 3b can potentiate phosphorylation of site 3a, by an enzyme such as glycogen synthase kinase-3.

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