Rho family GTPase signaling through type II p21-activated kinases

Chetty, Ashwin; Ha, Byung Hak; Boggon, Titus J.

doi:10.1007/s00018-022-04618-2

Cited by 4 publications

(1 citation statement)

References 188 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These proteins downstream of CaMK include Rho guanine exchange factors and Rho guanosine triphosphatases, which may activate many proteins, including Rho kinase (ROCK) and p21-activated kinase (PAK). Both PAK and ROCK activate LIM (Lin-11/Isl-1/Mec-3) domain–containing protein kinase 1 (LIMK1) ( 11 ), resulting in the inactivation of actin-depolymerizing factor (ADF)/cofilin, leading to actin polymerization and subsequent enlargement and stabilization of dendritic spines (Fig. 1A) ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Engineering memory with an extrinsically disordered kinase

Ripoli,

Dagliyan,

Renna

et al. 2023

Sci. Adv.

View full text Add to dashboard Cite

Synaptic plasticity plays a crucial role in memory formation by regulating the communication between neurons. Although actin polymerization has been linked to synaptic plasticity and dendritic spine stability, the causal link between actin polymerization and memory encoding has not been identified yet. It is not clear whether actin polymerization and structural changes in dendritic spines are a driver or a consequence of learning and memory. Using an extrinsically disordered form of the protein kinase LIMK1, which rapidly and precisely acts on ADF/cofilin, a direct modifier of actin, we induced long-term enlargement of dendritic spines and enhancement of synaptic transmission in the hippocampus on command. The activation of extrinsically disordered LIMK1 in vivo improved memory encoding and slowed cognitive decline in aged mice exhibiting reduced cofilin phosphorylation. The engineered memory by an extrinsically disordered LIMK1 supports a direct causal link between actin-mediated synaptic transmission and memory.

show abstract

Section: Introductionmentioning

confidence: 99%

Engineering memory with an extrinsically disordered kinase

Ripoli,

Dagliyan,

Renna

et al. 2023

Sci. Adv.

View full text Add to dashboard Cite

show abstract

Plexin D1 Negatively Regulates Macrophage-derived Foam Cell Migration via the Focal Adhesion Kinase/Paxillin Pathway

Li,

Niu,

Chen

et al. 2024

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

RHOA ^L57V drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling

Schaefer,

Hodge,

Zhang

et al. 2023

Sci. Signal.

View full text Add to dashboard Cite

Cancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at different locations from the mutational hotspots in the structurally and biochemically related RAS. Tyr 42 -to-Cys (Y42C) and Leu 57 -to-Val (L57V) substitutions are the two most prevalent RHOA mutations in diffuse gastric cancer (DGC). RHOA Y42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOA L57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1 , which encodes the cell adhesion protein E-cadherin, the expression of RHOA L57V , but not of wild-type RHOA, induced an abnormal morphology similar to that of patient-derived DGC organoids. RHOA L57V also exhibited a gain-of-function phenotype and promoted F-actin stress fiber formation and cell migration. RHOA L57V retained interaction with effectors but exhibited impaired RHOA-intrinsic and GAP-catalyzed GTP hydrolysis, which favored formation of the active GTP-bound state. Introduction of missense mutations at KRAS residues analogous to Tyr 42 and Leu 57 in RHOA did not activate KRAS oncogenic potential, indicating distinct functional effects in otherwise highly related GTPases. Both RHOA mutants stimulated the transcriptional co-activator YAP1 through actin dynamics to promote DGC progression; however, RHOA L57V additionally did so by activating the kinases IGF1R and PAK1, distinct from the FAK-mediated mechanism induced by RHOA Y42C . Our results reveal that RHOA L57V and RHOA Y42C drive the development of DGC through distinct biochemical and signaling mechanisms.

show abstract

Rho family GTPase signaling through type II p21-activated kinases

Cited by 4 publications

References 188 publications

Engineering memory with an extrinsically disordered kinase

Engineering memory with an extrinsically disordered kinase

Plexin D1 Negatively Regulates Macrophage-derived Foam Cell Migration via the Focal Adhesion Kinase/Paxillin Pathway

RHOA ^L57V drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling

Contact Info

Product

Resources

About

Rho family GTPase signaling through type II p21-activated kinases

Cited by 4 publications

References 188 publications

Engineering memory with an extrinsically disordered kinase

Engineering memory with an extrinsically disordered kinase

Plexin D1 Negatively Regulates Macrophage-derived Foam Cell Migration via the Focal Adhesion Kinase/Paxillin Pathway

RHOA L57V drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling

Contact Info

Product

Resources

About

RHOA ^L57V drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling