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| Depiction of functional domains of Parvin-beta(long) and Parvin-beta(short). NLS, nuclear localization sequence; ABS, actin binding sequence; CH, calponin homology. Adapted from Sepulveda and Wu, 2006. |
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Description | The major functional domains of Parvin-beta are two 'atypical' calponin homology (CH) domains, termed CH1 (106 amino acids) and CH2 (107 amino acids). Each CH domain contains two actin binding sequences (ABS), although Parvin-beta has not been shown to bind actin directly (Korenbaum et al., 2001; Sepulveda and Wu, 2006). Parvin-beta physically interacts with Dysferlin and ARHGEF6 (alpha-PIX) through the CH1 domain (Matsuda et al., 2005; Rosenberger et al., 2003) and with ILK and alpha-actinin through the CH2 domain (Yamaji et al., 2001; Yamaji et al., 2004). Parvin-beta was also recently reported to directly interact with AKT (Kimura et al., 2010). |
Expression | PARVB is essentially ubiquitously expressed. |
Localisation | Parvin-beta localises to focal adhesions but also to the nucleus, which is most likely due to NLS motifs in the N-terminal region (Mongroo et al., 2004; Johnstone et al., 2008). Parvin-beta is incorporated into focal adhesions as part of the heterotrimeric 'IPP complex'. The ternary complex contains 1 molecule of integrin linked kinase (ILK), 1 Parvin isoform, and 1 PINCH (LIMS) isoform, (Legate et al., 2006). Binding of Parvin-alpha and Parvin-beta to the kinase domain of ILK is mutually exclusive (Zhang et al., 2004). Formation of the IPP complex also dictates total protein levels of each component, as any excess ILK, Parvin, or PINCH not incorporated into IPP is degraded in a proteasome-dependent manner (Fukuda et al., 2003). |
Function | Parvin-beta participates in focal adhesion dynamics through involvement in the IPP complex. The high expression levels in cardiac and skeletal muscle suggest important function(s) in these organs. In skeletal muscle, it binds dysferlin at the sarcolemma and thus may be involved with membrane repair (Yamaji et al., 2001; Matsuda et al., 2005; Legate et al., 2006). Parvin-beta and Parvin-alpha appear to negatively regulate the expression of each other (Zhang et al., 2004; Johnstone et al., 2008). Parvin-beta may modulate signalling through ILK as overexpression of Parvin-beta reduced AKT (S473) and GSK3beta (S9) phosphorylation in response to EGF stimulation (Mongroo et al., 2004). Parvin-beta was recently reported to directly interact with AKT (Kimura et al., 2010), which may explain its effects on AKT phosphorylation. Parvin-beta interacts with ARHGEF6 (alpha-PIX), an exchange factor for RAC1, thus implicating Parvin-beta in regulation of RAC signalling downstream of integrin engagement (Rosenberger et al., 2003). Finally, Parvin-beta may affect metabolic pathways through promotion of CDK9-mediated phosphorylation and activation of PPARgamma transcriptional activity in the nucleus (Johnstone et al., 2008). Interestingly, Parvb knockout mice were recently generated. Whilst constitutive Parva null mice feature kidney and cardiovascular defects and die between E10.5 and E14.5 (Lange et al., 2009; Montanez et al., 2009), constitutive Parvb null mice are viable (Wickström et al., 2010), although a detailed phenotypic analysis has not yet been described. |
Homology | Human Parvin-beta is most closely related to Parvin-alpha [75% identity with Parvin-beta(short) and 67% identity with Parvin-beta(long)] and more distantly to Parvin-gamma [41% identity with both Parvin-beta(short) and Parvin-beta(long)]. |
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