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Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
- D. Cross, D. Alessi, P. Cohen, Mirjana Andjelkovich, B. Hemmings
- Biology, Medicine
- 28 December 1995
It is shown that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3, and it is demonstrated that PKB is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC). Expand
PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in Vivo(*)
- D. Alessi, A. Cuenda, Philip R. Cohen, D. T. Dudley, A. Saltiel
- Biology, Medicine
- The Journal of Biological Chemistry
- 17 November 1995
The results indicate that the activation of Raf is suppressed and that its inactivation is accelerated by a downstream component(s) of the MAP kinase pathway. Expand
Mechanism of activation of protein kinase B by insulin and IGF‐1.
It is demonstrated that activation of PKBalpha by insulin or insulin‐like growth factor‐1 (IGF‐1) results from phosphorylation of both Thr308 and Ser473, that phosphorylate of both residues is critical to generate a high level of P KBalpha activity and that the phosphorylated of Thr308 in vivo is not dependent on phosphorylations of Ser473 or vice versa. Expand
Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα
BACKGROUND Protein kinase B (PKB), also known as c-Akt, is activated rapidly when mammalian cells are stimulated with insulin and growth factors, and much of the current interest in this enzyme stems… Expand
The selectivity of protein kinase inhibitors: a further update.
Harmine has been identified as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro and the results have further emphasized the need for considerable caution in using small-molecule inhibitors of protein kinases to assess the physiological roles of these enzymes. Expand
LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR‐1
The results show that LKB1 functions as a master upstream protein kinase, regulating AMPK‐related kinases as well as AMPK, and may mediate the physiological effects of L KB1, including its tumour suppressor function. Expand
The nuts and bolts of AGC protein kinases
The AGC kinase subfamily of protein kinases contains 60 members, including PKA, PKG and PKC, and their mutation and/or dysregulation contributes to the pathogenesis of many human diseases, including cancer and diabetes. Expand
Mitogen‐ and stress‐activated protein kinase‐1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB
It is suggested that MSK1 may mediate the growth‐factor and stress‐induced activation of CREB, and exclude a role for MAPK AP‐K1 and MAPKAP‐K2/3 in this process. Expand
The PI3K-PDK1 connection: more than just a road to PKB.
The mechanism by which PKB is activated and the downstream actions of this multifunctional kinase are reviewed, as well as the evidence that PDK1 may be involved in the activation of protein kinases other than PKB, and the possibility that some of the currently postulated PKB substrates targets might in fact be phosphorylated byPDK1-regulated kinasesother than P KB. Expand
Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade
These results provide the first description of a physiological substrate for the LKB1 tumor suppressor and suggest that it functions as an upstream regulator of AMPK. Expand