RGD Reference Report - Adaptor protein LRAP25 mediates myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) regulation of LIMK1 protein in lamellipodial F-actin dynamics.

Advanced Search (OLGA)

General

Adaptor protein LRAP25 mediates myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) regulation of LIMK1 protein in lamellipodial F-actin dynamics.
Authors:	Lee, Irene Cheng Jie Leung, Thomas Tan, Ivan
Citation:	Lee IC, etal., J Biol Chem. 2014 Sep 26;289(39):26989-7003. doi: 10.1074/jbc.M114.588079. Epub 2014 Aug 8.
RGD ID:	13210541
Pubmed:	PMID:25107909 (View Abstract at PubMed)
PMCID:	PMC4175338 (View Article at PubMed Central)
DOI:	DOI:10.1074/jbc.M114.588079 (Journal Full-text)
Myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) has been shown to localize to the lamella of mammalian cells through its interaction with an adaptor protein, leucine repeat adaptor protein 35a (LRAP35a), which links it with myosin 18A (MYO18A) for activation of the lamellar actomyosin network essential for cell migration. Here, we report the identification of another adaptor protein LRAP25 that mediates MRCK association with LIM kinase 1 (LIMK1). The lamellipodium-localized LRAP25-MRCK complex is essential for the regulation of local LIMK1 and its downstream F-actin regulatory factor cofilin. Functionally, inhibition of either MRCK or LRAP25 resulted in a marked suppression of LIMK1 activity and down-regulation of cofilin phosphorylation in response to aluminum fluoride induction in B16-F1 cells, which eventually resulted in deregulation of lamellipodial F-actin and reorganization of cytoskeletal structures causing defects in cell polarization and motility. These biochemical and functional characterizations thus underline the functional relevance of the LRAP25-MRCK complex in LIMK1-cofilin signaling and the importance of LRAP adaptors as key determinants of MRCK cellular localization and downstream specificities.

Annotation Click to see Annotation Detail View

Gene Ontology Annotations Click to see Annotation Detail View

Molecular Function

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Cdc42bpa	Rat	protein binding	enables	IPI	UniProtKB:Q566R4	PMID:25107909	UniProt
Cdc42bpb	Rat	protein binding	enables	IPI	UniProtKB:Q566R4	PMID:25107909	UniProt
Fam89b	Rat	protein binding	enables	IPI	UniProtKB:O54874 and UniProtKB:Q7TT49	PMID:25107909	UniProt

Objects Annotated

Genes (Rattus norvegicus)

Cdc42bpa (CDC42 binding protein kinase alpha)

Cdc42bpb (CDC42 binding protein kinase beta)

Fam89b (family with sequence similarity 89, member B)

Additional Information

Gene Annotator (Functional Annotation) unavailable	Gene Annotator (Annotation Distribution) unavailable	Variant Visualizer (Genomic Variants) unavailble Variant Visualizer (Genomic Variants) unavailable
Gene Annotator (Functional Annotation)	Gene Annotator (Annotation Distribution)	Variant Visualizer (Genomic Variants)

InterViewer (Protein-Protein Interactions) unavailable	Gviewer (Genome Viewer) unavailable	Variant Visualizer (Damaging Variants) unavailble Variant Visualizer (Damaging Variants) unavailable
InterViewer (Protein-Protein Interactions)	GViewer (Genome Viewer)	Variant Visualizer (Damaging Variants)

Gene Annotator (Annotation Comparison) unavailable	OLGA (Gene List Generator) unavailable
Gene Annotator (Annotation Comparison)	OLGA (Gene List Generator)	Excel (Download)

MOET (Multi-Ontology Enrichement) unavailable	GOLF (Gene-Ortholog Location Finder) unavailable
MOET (Multi-Ontology Enrichement)	GOLF (Gene-Ortholog Location Finder)

Create Name:

Description:

Send us a Message

Adaptor protein LRAP25 mediates myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) regulation of LIMK1 protein in lamellipodial F-actin dynamics.