Calpain regulates N-terminal interaction of GSK-3ß with 14-3-3?, p53 and PKB but not with axin.
AuthorsGoñi-Oliver P, Avila J, Hernández F,
JournalNeurochem Int
PubMed ID21672591
'Calpain produces a truncation of GSK3ß that removes the N-terminal inhibitory domain. Here we analyze the effect of that truncation on protein-protein interaction. We pulled down GST-tagged proteins in the presence of full length GSK-3ß and calpain-cleaved GSK-3ß. Commercial GSK-3ß was first incubated with calpain for 2.5 min in vitro, ... More
Glycogen synthase kinase-3 inhibition disrupts nuclear factor-kappaB activity in pancreatic cancer, but fails to sensitize to gemcitabine chemotherapy.
AuthorsMamaghani S, Patel S, Hedley DW,
JournalBMC Cancer
PubMed ID19405981
'Aberrant activation NF-kappaB has been proposed as a mechanism of drug resistance in pancreatic cancer. Recently, inhibition of glycogen synthase kinase-3 has been shown to exert anti-tumor effects on pancreatic cancer cells by suppressing NF-kappaB. Consequently, we investigated whether inhibition of GSK-3 sensitizes pancreatic cancer cells to the chemotherapeutic agent ... More
Role of TAPP1 and TAPP2 adaptor binding to PtdIns(3,4)P2 in regulating insulin sensitivity defined by knock-in analysis.
AuthorsWullschleger S, Wasserman DH, Gray A, Sakamoto K, Alessi DR,
JournalBiochem J
PubMed ID21204784
'Insulin sensitivity is critically dependent on the activity of PI3K (phosphoinositide 3-kinase) and generation of the PtdIns(3,4,5)P(3) second messenger. PtdIns(3,4,5)P(3) can be broken down to PtdIns(3,4)P(2) through the action of the SHIPs (Src-homology-2-domain-containing inositol phosphatases). As PtdIns(3,4)P(2) levels peak after those of PtdIns(3,4,5)P(3), it has been proposed that PtdIns(3,4)P(2) controls ... More
Post-ischemic estradiol treatment reduced glial response and triggers distinct cortical and hippocampal signaling in a rat model of cerebral ischemia.
AuthorsPérez-Álvarez MJ, Maza Mdel C, Anton M, Ordoñez L, Wandosell F,
JournalJ Neuroinflammation
PubMed ID22747981
'Estradiol has been shown to exert neuroprotective effects in several neurodegenerative conditions, including cerebral ischemia. The presence of this hormone prior to ischemia attenuates the damage associated with such events in a rodent model (middle cerebral artery occlusion (MCAO)), although its therapeutic value when administered post-ischemia has not been assessed. ... More
Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1).
S6K1 (p70 ribosomal S6 kinase 1) is activated by insulin and growth factors via the PI3K (phosphoinositide 3-kinase) and mTOR (mammalian target of rapamycin) signalling pathways. S6K1 regulates numerous processes, such as protein synthesis, growth, proliferation and longevity, and its inhibition has been proposed as a strategy for the treatment ... More
Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase.
AuthorsTaurin S, Sandbo N, Qin Y, Browning D, Dulin NO,
JournalJ Biol Chem
PubMed ID16476742
Beta-catenin is a signaling molecule that promotes cell proliferation by the induction of gene transcription through the activation of T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcription factors. The canonical mechanism of the regulation of beta-catenin involves its phosphorylation by casein kinase 1 at the Ser-45 site and by glycogen synthase ... More
Phosphorylation of human respiratory syncytial virus P protein at serine 54 regulates viral uncoating.
AuthorsAsenjo A, González-Armas JC, Villanueva N,
JournalVirology
PubMed ID18706669
The human respiratory syncytial virus (HRSV) structural P protein, phosphorylated at serine (S) and threonine (T) residues, is a co-factor of viral RNA polymerase. The phosphorylation of S54 is controlled by the coordinated action of two cellular enzymes: a lithium-sensitive kinase, probably glycogen synthetase kinase (GSK-3) beta and protein phosphatase ... More
Glycogen synthase kinase-3 interacts with and phosphorylates estrogen receptor alpha and is involved in the regulation of receptor activity.
AuthorsMedunjanin S, Hermani A, De Servi B, Grisouard J, Rincke G, Mayer D,
JournalJ Biol Chem
PubMed ID16076840
Like other steroid hormone receptors, estrogen receptor-alpha (ERalpha) is a substrate for protein kinases, and phosphorylation has profound effects on the function and activity of this receptor. A number of different kinases have been implicated in ERalpha regulation. In this report we show by mutational analysis and in vitro kinase ... More
Kinase activities increase during the development of tauopathy in htau mice.
AuthorsKelleher I, Garwood C, Hanger DP, Anderton BH, Noble W,
JournalJ Neurochem
PubMed ID17908241
Hyperphosphorylated tau aggregates are the core constituent of neurofibrillary tangles. Recent research has shown a division between the presence of tangles, neurodegeneration and subsequent memory impairment, raising the possibility that an earlier pre-aggregated form of tau may be toxic. To gain further insight into the relationship between abnormal forms of ... More