NDLI: Regulation of the p21-activated kinase (PAK) by a human Gbeta -like WD-repeat protein, hPIP1.

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Regulation of the p21-activated kinase (PAK) by a human Gbeta -like WD-repeat protein, hPIP1.

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Regulation of the p21-activated kinase (PAK) by a human Gbeta -like WD-repeat protein, hPIP1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Xiong, W. C. Xia, C. Stafford, L. J. Marcus, S. Liu, M. Ma, W.
Description	Author Affiliation: Xia C ( Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, and Department of Medical Biochemistry and Genetics, Texas A&M University System Health Science Center, Houston, TX 77030, USA.);
Abstract	The family of p21-activated protein kinases (PAKs) is composed of serine-threonine kinases whose activity is regulated by the small guanosine triphosphatases (GTPases) Rac and Cdc42. In mammalian cells, PAKs have been implicated in the regulation of mitogen-activated protein cascades, cellular morphological and cytoskeletal changes, neurite outgrowth, and cell apoptosis. Although the ability of Cdc42 and Rac GTPases to activate PAK is well established, relatively little is known about the negative regulation of PAK or the identity of PAK cellular targets. Here, we describe the identification and characterization of a human PAK-interacting protein, hPIP1. hPIP1 contains G protein beta-like WD repeats and shares sequence homology with the essential fission yeast PAK regulator, Skb15, as well as the essential budding yeast protein, MAK11. Interaction of hPIP1 with PAK1 inhibits the Cdc42/Rac-stimulated kinase activity through the N-terminal regulatory domains of PAK1. Cotransfection of hPIP1 in mammalian cells inhibits PAK-mediated c-Jun N-terminal kinase and nuclear factor kappa B signaling pathways. Our results demonstrate that hPIP1 is a negative regulator of PAK and PAK signaling pathways.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Carrier Proteins Metabolism GTP-Binding Proteins Intracellular Signaling Peptides And Proteins Protein-Serine-Threonine Kinases Antagonists & Inhibitors Amino Acid Sequence Animals COS Cells Genetics Cell Size Cercopithecus Aethiops Cloning, Molecular Cytoskeleton Physiology Gene Expression Isoenzymes JNK Mitogen-Activated Protein Kinases Mice Mitogen-Activated Protein Kinases Molecular Sequence Data NF-kappa B Phospholipase C Beta Recombinant Fusion Proteins Tissue Distribution Type C Phospholipases Cdc42 GTP-Binding Protein P21-Activated Kinases Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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