Membrane targeting of p21-activated kinase 1 (PAK1) induces neurite outgrowth from PC12 cells

The EMBO Journal
R H DanielsG M Bokoch

Abstract

Rho-family GTPases regulate cytoskeletal dynamics in various cell types. p21-activated kinase 1 (PAK1) is one of the downstream effectors of Rac and Cdc42 which has been implicated as a mediator of polarized cytoskeletal changes in fibroblasts. We show here that the extension of neurites induced by nerve growth factor (NGF) in the neuronal cell line PC12 is inhibited by dominant-negative Rac2 and Cdc42, indicating that these GTPases are required components of the NGF signaling pathway. While cytoplasmically expressed PAK1 constructs do not cause efficient neurite outgrowth from PC12 cells, targeting of these constructs to the plasma membrane via a C-terminal isoprenylation sequence induced PC12 cells to extend neurites similar to those stimulated by NGF. This effect was independent of PAK1 ser/thr kinase activity but was dependent on structural domains within both the N- and C-terminal portions of the molecule. Using these regions of PAK1 as dominant-negative inhibitors, we were able to effectively inhibit normal neurite outgrowth stimulated by NGF. Taken together with the requirement for Rac and Cdc42 in neurite outgrowth, these data suggest that PAK(s) may be acting downstream of these GTPases in a signaling system which driv...Continue Reading

References

May 1, 1991·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·P R Gordon-Weeks
Dec 8, 1995·The Journal of Biological Chemistry·P D BurbeloA Hall
May 1, 1995·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·D RobertsonP Monaghan
Sep 1, 1994·Trends in Genetics : TIG·J Chant
Feb 1, 1994·Current Opinion in Neurobiology·D Bentley, T P O'Connor
Oct 18, 1996·The Journal of Biological Chemistry·G M BokochU G Knaus
Dec 13, 1996·The Journal of Biological Chemistry·C WuE Leberer
Feb 1, 1997·Current Opinion in Genetics & Development·E LebererM Whiteway
Feb 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·H BrzeskaE D Korn
Mar 1, 1997·Current Biology : CB·M A SellsJ Chernoff

❮ Previous
Next ❯

Citations

Oct 12, 2000·Journal of Cellular Physiology·K C MalcolmE van Obberghen-Schilling
Dec 14, 2002·Analytical Biochemistry·Andrea Gatti
Dec 14, 2002·Brain Research. Developmental Brain Research·Yi Hong ZhangLuc A Sabourin
Nov 13, 2002·Neurochemistry International·Bor Luen Tang
May 22, 2003·Progress in Neurobiology·Hitoshi YasudaRyuichi Kikkawa
Apr 15, 2003·Cancer Letters·Soo-Jung AhnDong-Young Noh
Oct 25, 2003·Cellular Signalling·Raymond E Menard, Raymond R Mattingly
Feb 27, 1999·Current Opinion in Cell Biology·P Aspenström
May 29, 2000·Current Opinion in Genetics & Development·D Toniolo, P D'Adamo
Sep 2, 1999·Trends in Biochemical Sciences·R H Daniels, G M Bokoch
Apr 16, 2002·The International Journal of Biochemistry & Cell Biology·Margareta Nikolic
Sep 23, 1998·The International Journal of Biochemistry & Cell Biology·U G Knaus, G M Bokoch
Jun 20, 2002·Journal of Biotechnology·Jörg Dennig, Emma Duncan
Nov 1, 2007·Nature Reviews. Molecular Cell Biology·Mark R MorganMark D Bass
May 19, 2000·The Biochemical Journal·A L Bishop, A Hall
Feb 13, 2001·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·T MurataY Nishiyama
Dec 12, 2001·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·M YanagisawaT Taga
Mar 15, 2001·European Journal of Biochemistry·G Paglini, A Cáceres
Oct 23, 2002·Journal of Neurochemistry·Gary Meyer, Eva L Feldman
May 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Céline Van den BroekeHerman W Favoreel
Aug 16, 2002·Molecular Biology of the Cell·Evangelia A Papakonstanti, Christos Stournaras
Oct 8, 1999·Molecular Biology of the Cell·M Spaargaren, J L Bos
May 8, 1999·Molecular Biology of the Cell·D KalmanJ M Bishop
Oct 12, 2000·Molecular Biology of the Cell·S DharmawardhaneG M Bokoch
Feb 17, 2006·Molecular Biology of the Cell·Huibin Yang, Raymond R Mattingly
Aug 15, 2008·Cerebral Cortex·Frédéric CauseretMargareta Nikolic
Aug 4, 1998·The EMBO Journal·A ObermeierL Lim
Mar 20, 2010·Molecular Biology and Evolution·Lesheng KongChris P Ponting
Sep 13, 2000·Molecular and Cellular Biology·H KatohM Negishi
Dec 28, 1999·Molecular and Cellular Biology·A SchürmannG M Bokoch
Mar 14, 2000·Molecular and Cellular Biology·O T FacklerB M Peterlin
Jan 5, 2002·Molecular and Cellular Biology·Chuntao DanAudrey Minden
Apr 10, 2002·Molecular and Cellular Biology·Hironori KatohManabu Negishi
Oct 1, 2003·Molecular and Cellular Biology·Jian QuAudrey Minden
Oct 16, 2003·Molecular and Cellular Biology·Nerina Gnesutta, Audrey Minden
Oct 31, 2003·Molecular and Cellular Biology·Guo-Lei ZhouJeffrey Field

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.