Disease relevance of PARVB

• Beta-parvin inhibits integrin-linked kinase signaling and is downregulated in breast cancer [1].

High impact information on PARVB

• Previously, we have reported that a novel integrin-linked kinase (ILK)-binding protein, affixin, is closely involved in the linkage between integrin and cytoskeleton in combination with ILK [2].
• Affixin interacts with alpha-actinin and mediates integrin signaling for reorganization of F-actin induced by initial cell-substrate interaction [2].
• These data suggest that both the N-terminal calponin homology (CH) and C-terminal coiled-coil domains are necessary for the ARHGEF6-PARVB binding [3].
• In this study, we demonstrate that gamma-parvin, one of three mammalian parvin family members, is specifically expressed in several lymphoid and monocytic cell lines in a complementary manner to affixin [4].
• Previously, we identified an integrin-linked kinase (ILK)-binding protein affixin (beta-parvin), which links initial integrin signals to rapid actin reorganization, and thus plays critical roles in fibroblast migration [4].

Biological context of PARVB

• Using immunoprecipitation with deletion mutants of dysferlin, we have identified that C-terminal region of dysferlin is an apparent binding site for affixin [5].
• The overexpression of a peptide corresponding to the alpha-actinin-binding site of affixin as well as the knockdown of endogenous affixin by small interference RNA resulted in the blockade of cell spreading [2].
• Possible role of ILK-affixin complex in integrin-cytoskeleton linkage during platelet aggregation [6].

Anatomical context of PARVB

• Dysferlin interacts with affixin (beta-parvin) at the sarcolemma [5].
• Affixin (beta-parvin) is a novel, integrin-linked kinase-binding protein that is involved in the linkage between integrin and the cytoskeleton [5].
• Colocalization of dysferlin and affixin was confirmed by immunofluorescence analysis using dysferlin-expressing C2 myoblasts [5].
• Overexpression of the COOH-terminal region of affixin, which is phosphorylated by ILK in vitro, blocks cell spreading at the initial stage, presumably by interfering with the formation of FAs and stress fibers [7].
• In CHOcells, affixin and ILK colocalize at FAs and at the tip of the leading edge, whereas in skeletal muscle cells they colocalize at the sarcolemma where cells attach to the basal lamina, showing a striped pattern corresponding to cytoplasmic Z-band striation [7].

Physical interactions of PARVB

• PARVB is known to interact with integrin-linked kinase (ILK) and is involved in the early stage of cell-substrate interaction through integrins [3].

Other interactions of PARVB

• In addition, we show that the interactions of ILK with alpha- and beta-parvin are mutually exclusive [8].
• We were surprised to find that loss of alpha-parvin, but not that of beta-parvin, markedly stimulated Rac activation and enhanced lamellipodium formation [8].
• The immunoreactivity of affixin was reduced in sarcolemma of MM and LGMD2B muscles, although the total amount of the affixin protein was normal [5].

References