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

  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},
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… 

The role of p21ras in receptor tyrosine kinase signalling.

Roles of PAK family kinases.

  • E. ManserL. Lim
  • Biology, Computer Science
    Progress in molecular and subcellular biology
  • 1999
In binding the active GTP-forms of Cdc42 and Racl, the α-and γ-PAKs also decrease intrinsic GTP hydrolysis and block action of GTPase activating proteins (GAPs).

Identification of a Putative Target for Rho as the Serine-Threonine Kinase Protein Kinase N

Activation of Rho may be linked directly to a serine-threonine kinase pathway, and this phosphorylation was blocked by treatment of cells with botulinum C3 exoenzyme.

The p21Rac/Cdc42-activated kinases (PAKs).

  • U. KnausG. Bokoch
  • Biology
    The international journal of biochemistry & cell biology
  • 1998

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.



A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42

The findings indicate that there may be a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation pathway.

A protein factor for ras p21-dependent activation of mitogen-activated protein (MAP) kinase through MAP kinase kinase.

  • T. ItohK. Kaibuchi Y. Takai
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1993

Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase.

The forming of complexes containing MAPKK activity and Raf-1 protein are dependent upon the activity of Ras, and the specific interaction of activated Ras with active MAP kinase kinase (MAPKK) was confirmed by direct assays.

Association between GTPase activators for Rho and Ras families

It is shown here that p190 can function as a GAP specifically for members of the rho family, and the formation of a complex between Ras-GAP and p190 in growth-factor stimulated cells may allow the coupling of signalling pathways that involve ras and rho GTPases.

Identification of the regulatory phosphorylation sites in pp42/mitogen‐activated protein kinase (MAP kinase).

The regulation of activity by dual phosphorylations at closely spaced threonyl and tyrosyl residues has a functional correlate in p34cdc2, and may be characteristic of a family of protein kinases regulating cell cycle transitions.

Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1

The Ras polypeptide and the amino-terminal regulatory domain of Raf-1 are shown to interact, directly in vitro and in a yeast expression system, and Mutations in and around the Ras effector domain impair Ras binding to Raf- 1(1-257) and Ras transforming activity in parallel.

A GDP dissociation inhibitor that serves as a GTPase inhibitor for the Ras-like protein CDC42Hs.

These findings establish an additional role for the GDI protein--namely, as a guanosine triphosphatase (GTPase) inhibitory protein for a Ras-like GTP binding protein.