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XB130/Tks5 scaffold protein interaction regulates Src-mediated cell proliferation and survival.

Moodley S, Hui Bai X, Kapus A, Yang B, Liu M - Mol. Biol. Cell (2015)

Bottom Line: Yeast two-hybrid screening suggests that XB130 interacts with another scaffold protein, Tks5.Structure-function studies showed that the fifth SH3 domain of Tks5 binds to the N-terminus of XB130, which contains polyproline-rich motifs.Furthermore, down-regulation of XB130 and/or Tks5 inhibited serum- and growth factor-induced Src activation and downstream phosphorylation of PI3K and Akt.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada.

No MeSH data available.


Related in: MedlinePlus

XB130 interacts with Tks5 and Src tyrosine kinase. (A) Schematic diagram of XB130 structure showing the Src homology 2 domain–binding motifs (SH2bm, green oval) and an SH3 domain–binding motif (SH3bm, yellow rectangle), two pleckstrin homology domains (PH, blue square), and a coiled-coiled region (purple rectangle). (B) Schematic diagram of Tks5 structure showing a phox homology domain (PX, red rectangle) and five SH3 domains (SH3, orange square). (C) CoIP of His-XB130 and Myc-Tks5 and immunoblot of XB130 and Tks5 in COS-7 cells. (D) CoIP of endogenous XB130, Tks5, and Src in BEAS-2B cells. Lane 4 was loaded with molecular weight markers. (E) Coimmunofluorescence staining shows that under unstimulated conditions, endogenous XB130 and Tks5 are both located in the cytoplasm and in the perinuclear region of BEAS-2B cells.
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Figure 1: XB130 interacts with Tks5 and Src tyrosine kinase. (A) Schematic diagram of XB130 structure showing the Src homology 2 domain–binding motifs (SH2bm, green oval) and an SH3 domain–binding motif (SH3bm, yellow rectangle), two pleckstrin homology domains (PH, blue square), and a coiled-coiled region (purple rectangle). (B) Schematic diagram of Tks5 structure showing a phox homology domain (PX, red rectangle) and five SH3 domains (SH3, orange square). (C) CoIP of His-XB130 and Myc-Tks5 and immunoblot of XB130 and Tks5 in COS-7 cells. (D) CoIP of endogenous XB130, Tks5, and Src in BEAS-2B cells. Lane 4 was loaded with molecular weight markers. (E) Coimmunofluorescence staining shows that under unstimulated conditions, endogenous XB130 and Tks5 are both located in the cytoplasm and in the perinuclear region of BEAS-2B cells.

Mentions: XB130 appears to be a classical example of the scaffold protein, containing various molecular-binding domains and acting as a signal transduction molecule to influence cell growth, survival, and migration (Xu et al., 2007; Lodyga et al., 2009, 2010; Snyder et al., 2011). DNA sequence homology data illustrate that XB130 belongs to the actin filament–associated protein (AFAP) family and is also known as actin filament–associated protein 1–like 2 (AFAP1L2; Xu et al., 2007; Snyder et al., 2011). Similar to AFAP, XB130 contains Src homology 2 (SH2) and Src homology 3 (SH3) binding motifs in its N-terminus (Figure 1A). XB130 also contains two pleckstrin homology (PH) domains for phosphatidylinositol lipid binding at cellular membranes (Figure 1A; Xu et al., 2007; Snyder et al., 2011). Unlike AFAP, XB130 lacks an actin-binding domain and is not associated with actin under basal conditions. However, epidermal growth factor (EGF), NNK (a nicotine-derived metabolite) and constitutively activated Rac1 (CA-Rac) induce XB130 translocation from the perinuclear cytoplasm to lamellipodia (Lodyga et al., 2010; Wu et al., 2015). Altered XB130 function has been shown to modulate several characteristics of cell migration, such as wound healing, cytoskeletal dynamics, cell spreading, and cell polarity (Lodyga et al., 2010).


XB130/Tks5 scaffold protein interaction regulates Src-mediated cell proliferation and survival.

Moodley S, Hui Bai X, Kapus A, Yang B, Liu M - Mol. Biol. Cell (2015)

XB130 interacts with Tks5 and Src tyrosine kinase. (A) Schematic diagram of XB130 structure showing the Src homology 2 domain–binding motifs (SH2bm, green oval) and an SH3 domain–binding motif (SH3bm, yellow rectangle), two pleckstrin homology domains (PH, blue square), and a coiled-coiled region (purple rectangle). (B) Schematic diagram of Tks5 structure showing a phox homology domain (PX, red rectangle) and five SH3 domains (SH3, orange square). (C) CoIP of His-XB130 and Myc-Tks5 and immunoblot of XB130 and Tks5 in COS-7 cells. (D) CoIP of endogenous XB130, Tks5, and Src in BEAS-2B cells. Lane 4 was loaded with molecular weight markers. (E) Coimmunofluorescence staining shows that under unstimulated conditions, endogenous XB130 and Tks5 are both located in the cytoplasm and in the perinuclear region of BEAS-2B cells.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 1: XB130 interacts with Tks5 and Src tyrosine kinase. (A) Schematic diagram of XB130 structure showing the Src homology 2 domain–binding motifs (SH2bm, green oval) and an SH3 domain–binding motif (SH3bm, yellow rectangle), two pleckstrin homology domains (PH, blue square), and a coiled-coiled region (purple rectangle). (B) Schematic diagram of Tks5 structure showing a phox homology domain (PX, red rectangle) and five SH3 domains (SH3, orange square). (C) CoIP of His-XB130 and Myc-Tks5 and immunoblot of XB130 and Tks5 in COS-7 cells. (D) CoIP of endogenous XB130, Tks5, and Src in BEAS-2B cells. Lane 4 was loaded with molecular weight markers. (E) Coimmunofluorescence staining shows that under unstimulated conditions, endogenous XB130 and Tks5 are both located in the cytoplasm and in the perinuclear region of BEAS-2B cells.
Mentions: XB130 appears to be a classical example of the scaffold protein, containing various molecular-binding domains and acting as a signal transduction molecule to influence cell growth, survival, and migration (Xu et al., 2007; Lodyga et al., 2009, 2010; Snyder et al., 2011). DNA sequence homology data illustrate that XB130 belongs to the actin filament–associated protein (AFAP) family and is also known as actin filament–associated protein 1–like 2 (AFAP1L2; Xu et al., 2007; Snyder et al., 2011). Similar to AFAP, XB130 contains Src homology 2 (SH2) and Src homology 3 (SH3) binding motifs in its N-terminus (Figure 1A). XB130 also contains two pleckstrin homology (PH) domains for phosphatidylinositol lipid binding at cellular membranes (Figure 1A; Xu et al., 2007; Snyder et al., 2011). Unlike AFAP, XB130 lacks an actin-binding domain and is not associated with actin under basal conditions. However, epidermal growth factor (EGF), NNK (a nicotine-derived metabolite) and constitutively activated Rac1 (CA-Rac) induce XB130 translocation from the perinuclear cytoplasm to lamellipodia (Lodyga et al., 2010; Wu et al., 2015). Altered XB130 function has been shown to modulate several characteristics of cell migration, such as wound healing, cytoskeletal dynamics, cell spreading, and cell polarity (Lodyga et al., 2010).

Bottom Line: Yeast two-hybrid screening suggests that XB130 interacts with another scaffold protein, Tks5.Structure-function studies showed that the fifth SH3 domain of Tks5 binds to the N-terminus of XB130, which contains polyproline-rich motifs.Furthermore, down-regulation of XB130 and/or Tks5 inhibited serum- and growth factor-induced Src activation and downstream phosphorylation of PI3K and Akt.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada.

No MeSH data available.


Related in: MedlinePlus