Mixed lineage kinase 3 promotes breast tumorigenesis via phosphorylation and activation of p21-activated kinase 1 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-01-21

AUTHORS

Subhasis Das, Rakesh Sathish Nair, Rajakishore Mishra, Gautam Sondarva, Navin Viswakarma, Hazem Abdelkarim, Vadim Gaponenko, Basabi Rana, Ajay Rana

ABSTRACT

Mixed lineage kinase 3 (MLK3), a MAP3K member has been envisioned as a viable drug target in cancer, yet its detailed function and signaling is not fully elucidated. We identified that MLK3 tightly associates with an oncogene, PAK1. Mammalian PAK1 being a Ste20 (MAP4K) member, we tested whether it is an upstream regulator of MLK3. In contrast to our hypothesis, MLK3 activated PAK1 kinase activity directly, as well as in the cells. Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3. Stable overexpression of PAK1S204A in breast cancer cells, impedes migration, invasion, and NFĸB activity. In vivo breast cancer cell tumorigenesis is significantly reduced in tumors expressing PAK1S204A mutant. These results suggest that mammalian PAK1 does not act as a MAP4K and MLK3-induced direct activation of PAK1 plays a key role in breast cancer tumorigenesis. More... »

PAGES

1-16

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41388-019-0690-0

DOI

http://dx.doi.org/10.1038/s41388-019-0690-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111567661

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30664689


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41388-019-0690-0'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41388-019-0690-0'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41388-019-0690-0'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41388-019-0690-0'


 

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283 schema:name Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, 60612, Chicago, IL, USA
284 Jesse Brown VA Medical Center, 60612, Chicago, IL, USA
285 University of Illinois Hospital &Health Sciences System Cancer Center, University of Illinois at Chicago, 60612, Chicago, IL, USA
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287 https://www.grid.ac/institutes/grid.448765.c schema:alternateName Central University of Jharkhand
288 schema:name Center for Life Sciences, School of Natural Sciences, Central University of Jharkhand, 835205, Ranchi, Jharkhand, India
289 rdf:type schema:Organization
 




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