Nckβ Adapter Regulates Actin Polymerization in NIH 3T3 Fibroblasts in Response to Platelet-Derived Growth Factor bb

Chen, Min; She, Hongyun; Kim, Airie; Woodley, David T.; Li, Wei

doi:10.1128/.20.21.7867-7880.2000

Cited by 15 publications

(20 citation statements)

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“…Moreover, Nck1 and Nck2 are to some extent functionally redundant and neither Nck1 nor Nck2 knock-out mice exhibit an apparent phenotype whereas double knock-out mice die in utero [ 2 ]. Nevertheless, some studies provided evidence for non-overlapping functions of Nck1 and Nck2 in certain cell types, including for example an exclusive regulation of actin polymerization in response to platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) treatment by Nck2 in fibroblasts and breast carcinoma cells (MTLn3) [ 3 , 4 ]. Moreover, the SH2 domain of Nck2 but not of Nck1 interacts with the docking protein Disabled-1 [ 5 ].…”

Section: The Nck Family Of Adapter Proteinsmentioning

confidence: 99%

“…Over the past years, Nck was shown to bind to several tyrosine-phosphorylated proteins via its SH2 domain. Thus, Nck isoproteins associate with activated receptor-tyrosine kinases such as the EGF receptor (EGFR) [ 8 , 9 ], vascular endothelial growth factor receptor (VEGFR) [ 10 - 13 ], PDGF receptor (PDGFR) [ 3 , 14 , 15 ], hepatocyte growth factor receptor (HGFR) [ 16 ], and with the Ephrin receptor EphB1 [ 17 , 18 ]. Also via its SH2 domain, Nck may associate with Dok (downstream of kinase signaling) proteins which seem to play a negative regulatory role in tyrosine kinase signaling [ 19 - 21 ].…”

Section: Nck Interaction Partners and Functional Implicationsmentioning

confidence: 99%

“…It was suggested that the SH2 domains of Nck1 and Nck2 differ with respect to their binding properties, especially since some non-overlapping functions have been observed [ 3 , 4 , 6 ]. In case of the PDGFR, the phospho-tyrosine residue pY751 was reported to be Nck1-specific [ 14 ], whereas pY1009 was Nck2-specific [ 3 ]. Moreover, only Nck2 associates with tyrosine-phosphorylated Disabled-1, an important adapter protein involved in brain cell positioning during development [ 5 ].…”

Section: Nck Interaction Partners and Functional Implicationsmentioning

confidence: 99%

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Nck adapter proteins: functional versatility in T cells

2009

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Nck is a ubiquitously expressed adapter protein that is almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins of Nck are functionally redundant in many aspects and differ in only few amino acids that are mostly located in the linker regions between the interaction modules. Nck proteins connect receptor and non-receptor tyrosine kinases to the machinery of actin reorganisation. Thereby, Nck regulates activation-dependent processes during cell polarisation and migration and plays a crucial role in the signal transduction of a variety of receptors including for instance PDGF-, HGF-, VEGF-and Ephrin receptors. In most cases, the SH2 domain mediates binding to the phosphorylated receptor or associated phosphoproteins, while SH3 domain interactions lead to the formation of larger protein complexes. In T lymphocytes, Nck plays a pivotal role in the T cell receptor (TCR)-induced reorganisation of the actin cytoskeleton and the formation of the immunological synapse. However, in this context, two different mechanisms and adapter complexes are discussed. In the first scenario, dependent on an activationinduced conformational change in the CD3ε subunits, a direct binding of Nck to components of the TCR/CD3 complex was shown. In the second scenario, Nck is recruited to the TCR complex via phosphorylated Slp76, another central constituent of the membrane proximal activation complex. Over the past years, a large number of putative Nck interactors have been identified in different cellular systems that point to diverse additional functions of the adapter protein, e.g. in the control of gene expression and proliferation.

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Section: The Nck Family Of Adapter Proteinsmentioning

confidence: 99%

Section: Nck Interaction Partners and Functional Implicationsmentioning

confidence: 99%

Section: Nck Interaction Partners and Functional Implicationsmentioning

confidence: 99%

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Nck adapter proteins: functional versatility in T cells

2009

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“…Nck‐2 is concentrated in membrane ruffles of spreading cells (Tu and Wu, unpublished observation), where DOCK180 is known to localize and function [12,13,24]. Recent studies by Chen et al have demonstrated that Nck‐2 regulates PDGF‐stimulated membrane ruffling [25]. Given the well documented importance of DOCK180 in the regulation of membrane ruffling and cell migration [12,13,24], the interaction of Nck‐2 with DOCK180 described in this paper suggests that the Nck‐2–DOCK180 complex likely plays an important role in cellular control of cell migration.…”

Section: Resultsmentioning

confidence: 99%

Identification and kinetic analysis of the interaction between Nck‐2 and DOCK180

Kucik

2001

FEBS Letters

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Nck-2 is a newly identified adapter protein comprising three N-terminal SH3 domains and one C-terminal SH2 domain. We have identified in a yeast two-hybrid screen DOCK180, a signaling protein implicated in the regulation of membrane ruffling and migration, as a binding protein for Nck-2. Surface plasmon resonance analyses reveal that the second and the third SH3 domains interact with the C-terminal region of DOCK180. The interactions mediated by the individual SH3 domains, however, are much weaker than that of the full length Nck-2. Furthermore, a point mutation that inactivates the second or the third SH3 domain dramatically reduced the interaction of Nck-2 with DOCK180, suggesting that both SH3 domains contribute to the DOCK180 binding. A major Nck-2 binding site, which is recognized primarily by the third SH3 domain, has been mapped to residues 1819^1836 of DOCK180. Two additional, albeit much weaker, Nck-2 SH3 binding sites are located to DOCK180 residues 1793^1810 and 1835^1852 respectively. Consistent with the mutational studies, kinetic analyses by surface plasmon resonance suggest that two binding events with equilibrium dissociation constants of 4.15 þ 1.9U U10 37 M and 3.24 þ 1.9U U10 39 M mediate the binding of GST-Nck-2 to GST fusion protein containing the C-terminal region of DOCK180. These studies identify a novel interaction between Nck-2 and DOCK180. Furthermore, they provide a detailed analysis of a protein complex formation mediated by multiple SH3 domains revealing that tandem SH3 domains significantly enhance the weak interactions mediated by each individual SH3 domain. ß

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“…HeLa cells were grown in minimum essential Eagle's medium (Sigma, St Louis, MO, USA) supplemented with 10% fetal bovine serum (Invitrogen, Burlington, Canada) at 37 °C in 5% CO 2 /95% O 2 . Subconfluent HeLa cells grown in 60 mm dishes were transfected with 1 µg HA‐tagged Nck‐1 construct (gift from W Li, LA California, previously described [32]) or empty vector (pRK5) using Lipofectamine‐Plus reagent (Invitrogen), according to the manufacturer's instructions. After 24 h of transfection, cells were subjected to different treatments to activate eIF2α‐kinases.…”

Section: Methodsmentioning

confidence: 99%

Nck‐1 selectively modulates eIF2αSer51 phosphorylation by a subset of eIF2α‐kinases

et al. 2007

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Protein synthesis results from the translation of mRNA into proteins. This process is dependent on numerous translational factors regulating the initiation, elongation and termination of translation (reviewed in [1]). Translation initiation is by far the most complex and is driven in part by the eukaryotic initiation factor 2 (eIF2) composed of three subunits (a, b and c). When bound to GTP, eIF2 is active and responsible for the transfer of the initiator methionyl tRNA (iMettRNA) to the 40S ribosomal subunit [2]. This step in translation is accompanied by the hydrolysis of GTP bound to eIF2 into GDP, with the recycling of the inactive eIF2-GDP into active eIF2-GTP being accomplished by the multimeric subunit-containing guanine nucleotide exchange factor eIF2B [1,3]. In addition, the activity of eIF2 is regulated by the phosphorylation of its a-subunit on Ser51 by eIF2a-kinases [4,5]. Phosphorylation of eIF2aSer51 increases the affinity of eIF2 for eIF2B and converts eIF2 from a substrate to an inhibitor of eIF2B, thus down-regulating protein

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Nckβ Adapter Regulates Actin Polymerization in NIH 3T3 Fibroblasts in Response to Platelet-Derived Growth Factor bb

Cited by 15 publications

References 0 publications

Nck adapter proteins: functional versatility in T cells

Nck adapter proteins: functional versatility in T cells

Identification and kinetic analysis of the interaction between Nck‐2 and DOCK180

Nck‐1 selectively modulates eIF2αSer51 phosphorylation by a subset of eIF2α‐kinases

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