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Prolactin-Dependent Regulation of the Actin Cytoskeleton by JAK2, SH2B1β, PAK1 and Filamin A

Rider, Leah Catherine
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310079439

Abstract Details

2011, Doctor of Philosophy, University of Toledo, Biology (Cell-Molecular Biology).
JAK2 is a receptor-associated tyrosine kinase responsible for signaling involving most of the cytokine family of receptors, including the prolactin (PRL) receptor (Murata, Noguchi et al. 1995; Argetsinger and Carter-Su 1996; Roy and Cathcart 1998; Parham, Chirica et al. 2002). p21-activated kinase (PAK1) is a serine-threonine kinase which participates in many important biological processes, including morphogenesis, cell survival, mitosis, transformation and regulation of the microtubule and actin cytoskeletons (Bokoch 2003; Zhao and Manser 2005; Kumar, Gururaj et al. 2006). Recently we have shown that PAK1 is a novel substrate for JAK2, which directly phosphorylates PAK1 in response to PRL in vivo and in vitro (Rider, Shatrova et al. 2007). SH2B1β is another substrate for JAK2, which binds to and increases the tyrosine kinase activity of JAK2 (Rui, Mathews et al. 1997; Rui and Carter-Su 1999). SH2B1β is an adaptor protein that participates in both cytokine and growth factor signaling and is involved in regulation of the actin cytoskeleton. SH2B1β promotes cytoskeletal rearrangement, inducing membrane ruffling and lamellipodia formation, as well as increasing cellular motility (Herrington, Diakonova et al. 2000; Diakonova, Gunter et al. 2002). We have recently shown that SH2B1β binds directly to F-actin and increases membrane ruffling in response to PRL (Rider, Tao et al. 2009). PAK1 has numerous actin-regulating substrates and we have found that one of these substrates - Filamin A (FLNa), an actin cross-linking protein – functions downstream of pTyr-PAK1. We show that FLNa also associates with SH2B1β in vivo and in vitro. We are interested in the role of both JAK2 substrates – PAK1 and SH2B1β – in the regulation of the actin cytoskeleton and cell motility. We hypothesize that JAK2, PAK1, SH2B1β and FLNa work in complex together in order to mediate cytoskeletal rearrangement in response to PRL.
Maria Diakonova, PhD (Advisor)
Max Funk, PhD (Committee Member)
William Taylor, PhD (Committee Member)
Lirim Shemshedini, PhD (Committee Member)
Ronald Viola, PhD (Committee Member)
130 p.
Cellular Biology
prolactin; actin; SH2B1&946; ; Filamin A; JAK2; PAK1; breast cancer; ruffling; invasion; migration

Recommended Citations

Citations

  • Rider, L. C. (2011). Prolactin-Dependent Regulation of the Actin Cytoskeleton by JAK2, SH2B1β, PAK1 and Filamin A [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310079439

    APA Style (7th edition)

  • Rider, Leah. Prolactin-Dependent Regulation of the Actin Cytoskeleton by JAK2, SH2B1β, PAK1 and Filamin A. 2011. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310079439.

    MLA Style (8th edition)

  • Rider, Leah. "Prolactin-Dependent Regulation of the Actin Cytoskeleton by JAK2, SH2B1β, PAK1 and Filamin A." Doctoral dissertation, University of Toledo, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1310079439

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Toledo and OhioLINK.