Paxillin: Adapting to Change

Brown, Michael C.; Turner, Christopher E.

doi:10.1152/physrev.00002.2004

Cited by 548 publications

(753 citation statements)

References 323 publications

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“…*Po0.05 and **Po0.005. threonine phosphorylation by activated kinases such as FAK, Src, JNK and p38 (Brown and Turner, 2004). In the present study, we identify a novel PRL-dependent interaction between the serine/threonine kinase Nek3 and paxillin (Figure 5a).…”

Section: Discussionsupporting

confidence: 51%

“…Although Western-blot analysis of equal amounts of protein in both cell lines showed no remarkable differences in basal Nek3 expression (Figure 3a), differences in PRL-mediated kinase activity and consequently phosphorylation of other proteins linked to cancer motility such as Vav2, PI3K, MAPK and paxillin may be significant. Paxillin is a multidomain adaptor that recruits both structural and signaling molecules to focal complexes, where its principal function is to affect efficient cellular migration (Brown and Turner, 2004). Paxillin is involved in multiple protein-protein interactions and mediates signaling crosstalk through its tyrosine and serine/ Figure 6 Knockdown of Nek3 attenuates the motility and invasion of T47D breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…The multidomain structure of paxillin and the lack of identifiable enzymatic motifs first identified it as an adaptor protein (Turner and Nek3 regulates breast cancer motility SL Miller et al Miller, 1994). Indeed, since its discovery, several proteins have been identified as binding partners (Brown and Turner, 2004). To investigate the PRL-dependent association between Nek3 and paxillin proteins, coimmunoprecipitation analyses of T47D WCL were conducted with Nek3 antibodies.…”

Section: Nek3 Contributes To Prl-mediated Rac1 Activationmentioning

confidence: 99%

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Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells

et al. 2007

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Prolactin (PRL) stimulates the cytoskeletal re-organization and motility of breast cancer cells. During PRL receptor signaling, Vav2 becomes phosphorylated and activated, an event regulated by the serine/threonine kinase Nek3. Given the regulatory role of Vav2, the function of Nek3 in PRL-mediated motility and invasion was examined. Overexpression of Nek3 in Chinese hamster ovary transfectants potentiated cytoskeletal re-organization in response to PRL. In contrast, downregulation of Nek3 expression by small-interfering RNA (siRNA) attenuated PRL-mediated cytoskeletal reorganization, activation of GTPase Rac1, cell migration and invasion of T47D cells. In addition, PRL stimulation induced an interaction between Nek3 and paxillin and significantly increased paxillin serine phosphorylation, whereas Nek3 siRNA-transfected cells showed a marked reduction in paxillin phosphorylation. Analysis of breast tissue microarrays also demonstrated a significant up-regulation of Nek3 expression in malignant versus normal specimens. These data suggest that Nek3 contributes to PRLmediated breast cancer motility through mechanisms involving Rac1 activation and paxillin phosphorylation.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Nek3 Contributes To Prl-mediated Rac1 Activationmentioning

confidence: 99%

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Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells

et al. 2007

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“…To understand the mechanisms underlying these diverse responses, in-depth characterization of individual proteins or pathways 11,12 , and collection of information about multiple components that concertedly form the presumed adhesome 13,14 , have been undertaken. Each of these approaches has limitations, and individually is unlikely to explain how the adhesion machinery senses environmental cues and responds to them.…”

mentioning

confidence: 99%

Functional atlas of the integrin adhesome

Zaidel-Bar¹,

Itzkovitz²,

et al. 2007

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A detailed depiction of the 'integrin adhesome', consisting of a complex network of 156 components linked together and modified by 690 interactions is presented. Different views of the network reveal several functional 'subnets' that are involved in switching on or off many of the molecular interactions within the network, consequently affecting cell adhesion, migration and cytoskeletal organization. Examination of the adhesome network motifs reveals a relatively small number of key motifs, dominated by three-component complexes in which a scaffolding molecule recruits both a signalling molecule and its downstream target. We discuss the role of the different network modules in regulating the structural and signalling functions of cell-matrix adhesions. Top-down and bottom-up approaches for studying the integrin adhesomeCell-extracellular matrix (ECM) interactions are mediated through specialized subcellular sites that contain specific adhesion receptors, cytoskeletal elements and a wide variety of interconnecting adaptor proteins [1][2][3] . These adhesion complexes permit cells to sense multiple extracellular signals that specify the chemical identity, geometry and physical properties of the ECM 4,5 . Thus, cells behave differently on two-and three-dimensional matrices 6 , distinguish between different ECM components 7 , can detect differences in adhesive ligand density 8 , and respond to mechanical perturbation and surface rigidity 9,10 . Competing Financial Interests:The authors declare no competing financial interests.Website -www.adhesome.org contains the adhesome database of components and interactions with an interface that allows dynamical navigation between hyperlinked subnets created for each component and for many network motifs within the adhesome network.Publisher's Disclaimer: Disclaimer: Nature Publishing Group has a collaboration with the Cell Migration Consortium for the creation and maintenance of the Cell Migration gateway (http://www.cellmigration.org/), but has no role in generating or curating the Cell Migration Consortium database content. As always, Nature Cell Biology Editors have been fully independent and solely responsible for the editorial content and peer review of this Analysis article. NIH Public Access Author ManuscriptNat Cell Biol. Author manuscript; available in PMC 2009 August 31. Published in final edited form as:Nat Cell Biol. 2007 August ; 9(8): 858-867. doi:10.1038/ncb0807-858. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptTo understand the mechanisms underlying these diverse responses, in-depth characterization of individual proteins or pathways 11,12 , and collection of information about multiple components that concertedly form the presumed adhesome 13,14 , have been undertaken. Each of these approaches has limitations, and individually is unlikely to explain how the adhesion machinery senses environmental cues and responds to them. However, combining data from the two approaches could produce new mechanistic insights into the structu...

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“…In addition to the eponymous paxillin, the androgen receptor-associated protein 55 kDa (ARA55) and leupaxin (LPXN) belong to the paxillin superfamily (Brown and Turner, 2004). All members of the paxillin family are characterized by the presence of two protein-protein interaction domains, namely LD motifs and LIM domains (Lipsky et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression

et al. 2009

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Recently, we could show that the focal adhesion protein leupaxin (LPXN) is expressed in human prostate carcinomas (PCa) and induces invasiveness of androgenindependent PCa cells. In this study we show that LPXN enhanced the progression of existing PCa in vivo by breeding transgenic mice with prostate-specific LPXN expression and TRAMP mice (transgenic adenocarcinoma of mouse prostate). Double transgenic LPXN/ TRAMP mice showed a significant increase in poorly differentiated PCa and distant metastases as compared with control TRAMP mice. Additional studies on primary PCa cells generated from both transgenic backgrounds confirmed the connection regarding LPXN overexpression and increased motility and invasiveness of PCa cells. One mediator of LPXN-induced invasion was found to be the cell-cell adhesion protein p120catenin (p120CTN). Both in vitro and in vivo experiments revealed that p120CTN expression negatively correlates with LPXN expression, followed by a redistribution of b-catenin. Downregulation of LPXN using small interfering RNAs (siRNAs) resulted in a membranous localization of b-catenin, whereas strong nuclear accumulation of b-catenin was observed in p120CTN knockdown cells leading to enhanced transcription of the b-catenin target gene matrix metalloprotease-7. In conclusion, the present results indicate that LPXN enhances the progression of PCa through downregulation of p120CTN expression and that LPXN could function as a marker for aggressive PCa in the future.

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Paxillin: Adapting to Change

Cited by 548 publications

References 323 publications

Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells

Nek3 kinase regulates prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells

Functional atlas of the integrin adhesome

Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression

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