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• W2004227669 endingPage "1243" @default.
• W2004227669 startingPage "1231" @default.
• W2004227669 abstract "Abstract Prolactin (PRL) regulates cytoskeletal rearrangement and cell motility. PRL-activated Janus tyrosine kinase 2 (JAK2) phosphorylates the p21-activated serine-threonine kinase (PAK)1 and the Src homology 2 (SH2) domain-containing adapter protein SH2B1β. SH2B1β is an actin-binding protein that cross-links actin filaments, whereas PAK1 regulates the actin cytoskeleton by different mechanisms, including direct phosphorylation of the actin-binding protein filamin A (FLNa). Here, we have used a FLNa-deficient human melanoma cell line (M2) and its derivative line (A7) that stably expresses FLNa to demonstrate that SH2B1β and FLNa are required for maximal PRL-dependent cell ruffling. We have found that in addition to two actin-binding domains, SH2B1β has a FLNa-binding domain (amino acids 200–260) that binds directly to repeats 17–23 of FLNa. The SH2B1β-FLNa interaction participates in PRL-dependent actin rearrangement. We also show that phosphorylation of the three tyrosines of PAK1 by JAK2, as well as the presence of FLNa, play a role in PRL-dependent cell ruffling. Finally, we show that the actin- and FLNa-binding-deficient mutant of SH2B1β (SH2B1β 3Δ) abolished PRL-dependent ruffling and PRL-dependent cell migration when expressed along with PAK1 Y3F (JAK2 tyrosyl-phosphorylation-deficient mutant). Together, these data provide insight into a novel mechanism of PRL-stimulated regulation of the actin cytoskeleton and cell motility via JAK2 signaling through FLNa, PAK1, and SH2B1β. We propose a model for PRL-dependent regulation of the actin cytoskeleton that integrates our findings with previous studies." @default.
• W2004227669 created "2016-06-24" @default.
• W2004227669 creator A5062118117 @default.
• W2004227669 creator A5065846931 @default.
• W2004227669 date "2011-07-01" @default.
• W2004227669 modified "2023-09-27" @default.
• W2004227669 title "Adapter Protein SH2B1β Binds Filamin A to Regulate Prolactin-Dependent Cytoskeletal Reorganization and Cell Motility" @default.
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• W2004227669 doi "https://doi.org/10.1210/me.2011-0056" @default.
• W2004227669 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3125092" @default.

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