A brain serine/threonine protein kinase activated by Cdc42 and Rac1

@article{Manser1994ABS,
  title={A brain serine/threonine protein kinase activated by Cdc42 and Rac1},
  author={Edward Manser and Thomas Leung and Harfizah Salihuddin and Zhuo-shen Zhao and Louis Lim},
  journal={Nature},
  year={1994},
  volume={367},
  pages={40-46}
}
A new brain serine/threonine protein kinase may be a target for the p21 ras -related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways. The kinase complexes specifically with activated (GTP-bound) p21, inhibiting p21 GTPase activity and leading to kinase autophosphorylation and activation. Autophosphorylated kinase has a decreased affinity for Cdc42/Rac, freeing the p21 for further stimulatory activities or… 

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The p21Rac/Cdc42-activated kinases (PAKs).

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Rho Family GTPases Regulate p38 Mitogen-activated Protein Kinase through the Downstream Mediator Pak1 (*)

Rac and Cdc42 appear to regulate a protein kinase cascade initiated at the level of Pak and leading to activation of p38 and JNK, and a dominant negative Pak1 suppresses both interleukin-1- and Rac/Cdc42-induced p38 activity.

A GTPase-independent Mechanism of p21-activated Kinase Activation

The results demonstrate a novel GTPase-independent mechanism of PAK activation and suggest that PAK(s) may be important mediators of the biological effects of sphingolipids.

The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338

The results indicate that signal transduction through Raf-1 depends on both Ras and the activation of the Pak pathway, and a mechanism could exist through which one Ras effector pathway can be influenced by another.

Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members

It is found that overexpression of the Ste20-related enzymes p21-activated kinase 1 (PAK1) and PAK2 in 293 cells is sufficient to activate JNK/SAPK and to a lesser extent p38 MAP kinase but not ERK2, suggesting a permissive role for Rac in the control of the ERK pathway.

The Prototype Rho-Associated Kinase PAK

A number of studies show PAK is implicated disease states, as a result PAK family kinases are becoming good candidates for drug development.

A Novel Serine/Threonine Kinase Binding the Ras-related RhoA GTPase Which Translocates the Kinase to Peripheral Membranes (*)

The isolation of a rat cDNA encoding a 150-kDa protein, which specifically binds RhoA in its GTP form and contains an N-terminal serine/threonine kinase domain highly related to the human myotonic dystrophy kinase and a cysteine-rich domain toward the C terminus is reported.
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