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Status: Bibliographieeintrag

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Verfasst von:Chase, Amanda [VerfasserIn]   i
 Wombacher, Rebecka [VerfasserIn]   i
 Fackler, Oliver Till [VerfasserIn]   i
Titel:Intrinsic properties and plasma membrane trafficking route of Src family kinase SH4 domains sensitive to retargeting by HIV-1 Nef
Verf.angabe:Amanda J. Chase, Rebecka Wombacher, and Oliver T. Fackler
E-Jahr:2018
Jahr:March 27. 2018
Umfang:17 S.
Fussnoten:Gesehen am 11.04.2019
Titel Quelle:Enthalten in: The journal of biological chemistry
Ort Quelle:Bethesda, Md. : Soc., 1905
Jahr Quelle:2018
Band/Heft Quelle:293(2018), 20, Seite 7824-7840
ISSN Quelle:1083-351X
Abstract:The HIV type 1 pathogenicity factor Nef enhances viral replication by modulating multiple host cell pathways, including tuning the activation state of infected CD4 T lymphocytes to optimize virus spread. For this, Nef inhibits anterograde transport of the Src family kinase (SFK) Lck toward the plasma membrane (PM). This leads to retargeting of the kinase to the trans-Golgi network, whereas the intracellular transport of a related SFK, Fyn, is unaffected by Nef. The 18-amino acid Src homology 4 (SH4) domain membrane anchor of Lck is necessary and sufficient for Nef-mediated retargeting, but other details of this process are not known. The goal of this study was therefore to identify characteristics of SH4 domains responsive to Nef and the transport machinery used. Screening a panel of SFK SH4 domains revealed two groups that were sensitive or insensitive for trans-Golgi network retargeting by Nef as well as the importance of the amino acid at position 8 for determining Nef sensitivity. Anterograde transport of Nef-sensitive domains was characterized by slower delivery to the PM and initial targeting to Golgi membranes, where transport was arrested in the presence of Nef. For Nef-sensitive SH4 domains, ectopic expression of the lipoprotein binding chaperone Unc119a or the GTPase Arl3 or reduction of their endogenous expression phenocopied the effect of Nef. Together, these results suggest that, analogous to K-Ras, Nef-sensitive SH4 domains are transported to the PM by a cycle of solubilization and membrane insertion and that intrinsic properties define SH4 domains as cargo of this Nef-sensitive lipoprotein binding chaperone-GTPase transport cycle.
DOI:doi:10.1074/jbc.RA118.002794
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag ; Resolving-System: https://doi.org/10.1074/jbc.RA118.002794
 Volltext: http://www.jbc.org/content/293/20/7824
 DOI: https://doi.org/10.1074/jbc.RA118.002794
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:anterograde transport
 HIV
 host-pathogen interaction
 lipid binding protein
 lipoprotein binding chaperone
 membrane transport
 Nef
 Src
 Src family kinase
K10plus-PPN:1663133433
Verknüpfungen:→ Zeitschrift

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