Phosphorylation and reorganization of vimentin by p21‐activated kinase (PAK)

  title={Phosphorylation and reorganization of vimentin by p21‐activated kinase (PAK)},
  author={Hidemasa Goto and Kazushi Tanabe and Edward Manser and Louis Lim and Yoshihiro Yasui and Masaki Inagaki},
  journal={Genes to Cells},
Background: Intermediate filament (IF) is one of the three major cytoskeletal filaments. Vimentin is the most widely expressed IF protein component. The Rho family of small GTPases, such as Cdc42, Rac and Rho, are thought to control the organization of actin filaments as well as other cytoskeletal filaments. 

Involvement of Rac/Cdc42/PAK pathway in cytoskeletal rearrangements.

A list of PAKs substrates and binding partners implicated directly and indirectly in cytoskeletal reorganization is presented and perturbations of the Rac/Cdc42/PAK pathway leading to tumorigenesis and neurodegenerative diseases are reviewed.

Vimentin intermediate filaments modulate the motility of mitochondria

The vimentin N-terminal domain contains the sequence responsible for the interaction with mitochondria and contributes to their anchoring in cytoplasm.

Substrate stiffness regulates solubility of cellular vimentin

The present results show for the first time that cells cultured on different stiffness substrates contain detergent-soluble vimentin.

Intermediate filaments mediate cytoskeletal crosstalk

Understanding the molecular basis of this cytoskeletal crosstalk is essential for determining the mechanisms that underlie many cell-biological phenomena.

Vimentin organization modulates the formation of lamellipodia

The disassembly and withdrawal of vimentin intermediate filaments from the plasma membrane induces membrane ruffling and the formation of a lamellipodium and this formation is inhibited when VIF are present.

Vimentin intermediate filament reorganization by Cdc42: involvement of PAK and p70 S6 kinase.

Cdc42V12 induces the reorganization of vimentin IFs in Hela cells, and such reorganization is independent of actin and microtubule status, and involves PAK and, in a novel cytoskeletal role, p70 S6K.

Dissociation of Crk-associated substrate from the vimentin network is regulated by p21-activated kinase on ACh activation of airway smooth muscle.

The PAK-mediated dissociation of CAS from the vimentin network may participate in the cellular processes that affect active force development during ACh activation of tracheal smooth muscle tissues.

RAB7A Regulates Vimentin Phosphorylation through AKT and PAK

It is found that RAB7A is able to regulate AKT (also called protein kinase B or PKB) and PAK1 (P21-Activated Kinase 1) and several of their downstream effectors and the processes they regulate, suggesting that R AB7A could have a role in a number of cancer hallmarks.

Critical Role of Vimentin Phosphorylation at Ser-56 by p21-activated Kinase in Vimentin Cytoskeleton Signaling*

The results suggest that vimentin phosphorylation at Ser-56 may inversely regulate PAK activation possibly via the increase in the amount of soluble CAS upon agonist stimulation of smooth muscle cells.



Dynamic property of intermediate filaments: Regulation by phosphorylation

Site‐specific phosphorylation of intermediate filament (IF) proteins on serine and threonine residues leads to alteration of the filament structure, in vitro and in vivo. Protein kinases involved in

Rho as a regulator of the cytoskeleton.

Intermediate filament dynamics.

Regulation of intermediate filament organization during cytokinesis: Possible roles of Rho‐associated kinase

Intermediate filaments (IFs), which form the structural framework of cytoskeleton, have been found to be dramatically reorganized during mitosis. Some protein kinases activated in mitosis are thought

p21-activated kinase PAK phosphorylates desmin at sites different from those for Rho-associated kinase.

It is reported that desmin serves as an excellent substrate for PAK in vitro and different site-specific phosphorylation of desmin via two divergent protein kinases downstream of Rho family GTPases would seem to increase the regulatory potential for organization of desmine filaments.

Phosphorylation-dependent control of structures of intermediate filaments: a novel approach using site- and phosphorylation state-specific antibodies.

State- and phosphorylation state-specific antibodies for IF proteins can visualize spatial and temporal distribution of site-specific IF protein phosphorylations in the cell.

Balance between Activities of Rho Kinase and Type 1 Protein Phosphatase Modulates Turnover of Phosphorylation and Dynamics of Desmin/Vimentin Filaments*

The results indicate that Rho kinase is activated not only in mitotic cells but also interphase ones, and phosphorylates intermediate filament proteins, although the apparent phosphorylation level is diminished to an undetectable level due to the constitutive action of type 1 protein phosphatase.

Pak to the future.