ArticlePloS one2009
Interaction with LC8 is required for Pak1 nuclear import and is indispensable for zebrafish development.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
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- Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos.Development (Cambridge, England) · 2024Article
- Group I PAKs in myelin formation and repair of the central nervous system: what, when, and how.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Dynein Light Chain DLC-1 Facilitates the Function of the Germline Cell Fate Regulator GLD-1 inGenetics · 2019Article
- Article
- The established and the predicted roles of dynein light chain in the regulation of mitochondrial apoptosis.Cell cycle (Georgetown, Tex.) · 2018Article
- PAK1 translocates into nucleus in response to prolactin but not to estrogen.Biochemical and biophysical research communications · 2016Article
- Dynein Light Chain LC8 Is Required for RNA Polymerase I-Mediated Transcription in Trypanosoma brucei, Facilitating Assembly and Promoter Binding of Class I Transcription Factor A.Molecular and cellular biology · 2016Article
- Multivalent IDP assemblies: Unique properties of LC8-associated, IDP duplex scaffolds.FEBS letters · 2015Review
- Republished: tracing PAKs from GI inflammation to cancer.Postgraduate medical journal · 2014Article
- Molecular pathways: targeting RAC-p21-activated serine-threonine kinase signaling in RAS-driven cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Review
- A Pak1/Erk signaling module acts through Gata6 to regulate cardiovascular development in zebrafish.Developmental cell · 2014Article
- PAK signalling during the development and progression of cancer.Nature reviews. Cancer · 2014Review
- Rho, nuclear actin, and actin-binding proteins in the regulation of transcription and gene expression.Small GTPases · 2014Review
- Pak1 kinase links ErbB2 to β-catenin in transformation of breast epithelial cells.Cancer research · 2013Article
- Molecular pathways: targeting p21-activated kinase 1 signaling in cancer--opportunities, challenges, and limitations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Review
- The versatile molecular complex component LC8 promotes several distinct steps of flagellar assembly.The Journal of cell biology · 2012Article
- PAK family kinases: Physiological roles and regulation.Cellular logistics · 2012Article
- The PAKs come of age: Celebrating 18 years of discovery.Cellular logistics · 2012Article
- Untangling the complexity of PAK1 dynamics: The future challenge.Cellular logistics · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Pak1 (p21 activated kinase 1) is a serine/threonine kinase implicated in regulation of cell motility and survival and in malignant transformation of mammary epithelial cells. In addition, the dynein light chain, LC8, has been described to cooperate with Pak1 in malignant transformation of breast cancer cells. Pak1 itself may aid breast cancer development by phosphorylating nuclear proteins, including estrogen receptor alpha. Recently, we showed that the LC8 binding site on Pak1 is adjacent to the nuclear localization sequence (NLS) required for Pak1 nuclear import. Here, we demonstrate that the LC8-Pak1 interaction is necessary for epidermal growth factor (EGF)-induced nuclear import of Pak1 in MCF-7 cells, and that this event is contingent upon LC8-mediated Pak1 dimerization. In contrast, Pak2, which lacks an LC8 binding site but contains a nuclear localization sequence identical to that in Pak1, remains cytoplasmic upon EGF stimulation of MCF-7 cells. Furthermore, we show that severe developmental defects in zebrafish embryos caused by morpholino injections targeting Pak are partially rescued by co-injection of wild-type human Pak1, but not by co-injection of mutant Pak1 mRNA disrupting either the LC8 binding or the NLS site. Collectively, these results suggest that LC8 facilitates nuclear import of Pak1 and that this function is indispensable during vertebrate development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.