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PMID: 15193260 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes.

Cancer cell ·Vol. 5 ·No. 6 ·2004-06-00 ·Pages 575-85

Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R

Abstract

We identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosphorylates both proteins. Phosphorylation of BimL by Pak1 prevents it from interacting with and inactivation of Bcl-2, an antiapoptotic protein. Overexpression of DLC1 but not DLC1-Ser88Ala mutant promotes cancerous properties of breast cancer cells. DLC1 protein level is elevated in more than 90% of human breast tumors. The regulation of cell survival functions by Pak1-DLC1 interaction represents a novel mechanism by which a signaling kinase might regulate the cancerous phenotypes.

MeSH Terms

Alanine/chemistry Apoptosis Blotting, Western Breast Neoplasms/pathology Carrier Proteins/pharmacology Cell Cycle Cell Division Cell Line, Tumor Cell Survival Cell Transformation, Neoplastic Drosophila Proteins Dyneins Flow Cytometry Gene Expression Regulation, Neoplastic Glutathione Transferase/metabolism Humans Immunohistochemistry Microscopy, Fluorescence Mutation Neoplasms/pathology Phenotype Phosphorylation Plasmids/metabolism Protein Binding Protein Serine-Threonine Kinases/metabolism Protein Structure, Tertiary Serine/chemistry Signal Transduction Time Factors Two-Hybrid System Techniques Up-Regulation p21-Activated Kinases

Chemicals

Carrier Proteins Drosophila Proteins Serine Glutathione Transferase Protein Serine-Threonine Kinases p21-Activated Kinases Dyneins Alanine

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Vadlamudi Ratna K

Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Bagheri-Yarmand Rozita

Yang Zhibo

Balasenthil Seetharaman

Nguyen Diep

Sahin Aysegul A

den Hollander Petra

Kumar Rakesh

Article Info

Journal

Cancer cell

Abbr.

Cancer Cell

ISSN

1535-6108

DOI

10.1016/j.ccr.2004.05.022

Published

2004-06-00

Pages

575-85

Language

English

Region

United States

NLM ID

101130617

Subset

Grants

NCI NIH HHS · CA80066 · United States

NCI NIH HHS · CA90970 · United States

Corrections

ErratumIn

External Links

PubMed source DOI: 10.1016/j.ccr.2004.05.022 View journal details

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Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes.

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