(Download) "Prolactin-Dependent Regulation of the Actin Cytoskeleton by JAK2, SH2B1β, PAK1 and Filamin A" by Leah Catherine Rider * eBook PDF Kindle ePub Free
eBook details
- Title: Prolactin-Dependent Regulation of the Actin Cytoskeleton by JAK2, SH2B1β, PAK1 and Filamin A
- Author : Leah Catherine Rider
- Release Date : January 19, 2013
- Genre: Science & Nature,Books,Professional & Technical,Medical,
- Pages : * pages
- Size : 11999 KB
Description
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.
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