Disease relevance of PXN

• Together with the previous observation that paxillin is a major substrate of pp60src in Rous sarcoma virus-transformed cells (Glenney, J. R., and L. Zokas. 1989. J. Cell Biol. 108:2401-2408), this interaction with vinculin suggests paxillin may be a key component in the control of focal adhesion organization [1].
• To determine whether increased FAK and paxillin protein concentrations are associated with hypertrophy and/or new fiber formation, two additional experiments were performed [2].
• Second, FAK (112% and 611%) and paxillin (87% and 431%) protein concentrations per unit of total protein in the soleus muscle increased at 1 and 8 days after surgical ablation of the synergistic gastrocnemius muscle (a model of hypertrophy without hyperplasia) [2].

High impact information on PXN

• This phenotype is also seen with ectopic expression of beta1 integrin, paxillin, or activated FAK (CD2 FAK) and therefore appears to result from enhanced integrin-mediated signaling [3].
• YPP150, paxillin, and tensin appear to be enriched in the cell contact fractions containing adhesion plaques and invadopodia relative to the cell body fraction, but are also present in the soluble supernate fraction [4].
• Paxillin: a new vinculin-binding protein present in focal adhesions [1].
• Paxillin purified from chicken gizzard smooth muscle migrates as a diffuse band on SDS-PAGE gels with a molecular mass of 65-70 kD [1].
• The 68-kD protein (paxillin) is a cytoskeletal component that localizes to the focal adhesions at the ends of actin stress fibers in chicken embryo fibroblasts [1].

Biological context of PXN

• Characterization of tyrosine phosphorylation of paxillin in vitro by focal adhesion kinase [5].
• The paxillin gene was localized to chromosome 12q24 by fluorescence in situ hybridization analysis [6].
• Moreover, a bacterially expressed recombinant glutathione S-transferase (GST)-CrkSH2 fragment bound paxillin in vitro with a subnanomolar affinity, suggesting that the SH2 domain of v-Crk is sufficient for binding [7].
• The adapter protein paxillin has been implicated in the regulation of cytoskeletal organization and cell motility [8].
• The role of tyr-31 and tyr-118 phosphorylation of paxillin in smooth muscle was evaluated by introducing plasmids encoding wild type paxillin or paxillin mutants F31, F118 or F31/118 (phenylalanine substitution at tyrosine sites 31, 118) into tracheal smooth muscle strips by reversible permeabilization, and incubating the tissues for 2 days [8].

Anatomical context of PXN

• As a first step toward assessing the function of paxillin phosphorylation on Tyr-118, a Y118F paxillin cDNA construct was transiently transfected into NIH 3T3 cells [5].
• The response of peripheral blood vessels to adrenergic and cholinergic agonists was examined 1, 3, 7, and 21 d after hens were treated with a single intramuscular injection of 2.5 mg/kg cyclic phenyl saligenin phosphate (PSP) or 0.10 mg/kg paraoxon (PXN) [9].
• Localization of paxillin, a focal adhesion protein, to smooth muscle dense plaques, and the myotendinous and neuromuscular junctions of skeletal muscle [10].
• In addition, paxillin was identified at the rat diaphragm neuromuscular junction [10].
• Expression of non-phosphorylatable paxillin mutants in canine tracheal smooth muscle inhibits tension development [8].

Associations of PXN with chemical compounds

• PSP treatment elevated the levels of norepinephrine and epinephrine throughout the study, while PXN treatment depressed the levels of these catecholamines [11].
• In the present study, acetylcholine (ACh)-stimulation of tracheal smooth muscle tissues increased paxillin phosphorylation at tyr-31 and tyr-118 by three- to fourfold [8].
• Two other components of focal contacts, paxillin and zyxin, were also co-localized with concentrated phosphotyrosine residues at sites that resemble focal contacts [12].
• Levels of the related protein, proline-rich tyrosine kinase 2 (Pyk2) and the FAK substrate paxillin, were unaffected by the addition of oligonucleotides, whereas FAK expression was reduced by 70% [13].

Other interactions of PXN

• These two organophosphates (OPs) cause different clinical effects in exposed animals, as PSP causes organophosphate-induced delayed neuropathy (OPIDN) and PXN causes acute poisoning through inhibition of acetylcholinesterase [9].
• Moreover, cell spreading during restitution of normal morphology did not require detectable tyrosine phosphorylation of pp125FAK, or its potential substrate paxillin, suggesting that pp125FAK may function more in the turnover of focal adhesions than in their assembly [14].
• The expression of wild type paxillin had no significant affect on force or myosin light chain phosphorylation [8].
• ADP-ribosylation factor GTPase-activating proteins (ARFGAPs) of the G-protein-coupled receptor kinase interactor 1/p95 paxillin kinase linker/p95-ARFGAP Pak-interacting exchange factor paxillin-binding protein (APP)-1 family are multidomain proteins, which interact functionally with both ARF and Rac GTPases [15].
• Association of focal adhesion kinase with fibronectin and paxillin is required for precartilage condensation of chick mesenchymal cells [16].

Analytical, diagnostic and therapeutic context of PXN

• The levels of plasma catecholamines were measured by high-performance liquid chromatograpy (HPLC) and indicated a different effect with PSP, which causes OPIDN, and PXN, which does not [11].
• FAK (77 and 81%) and paxillin (206 and 202%) protein concentrations per unit of total protein in Western blots increased significantly after 1.5 and 7 days, but not after 13 days, of stretch-induced hypertrophy-hyperplasia of the ALD muscle [2].

References