Expression Cloning of Signaling Proteins Regulated by Cell Adhesion

2006 ◽  
pp. 155-166 ◽  
Author(s):  
Michelle L. Matter ◽  
Joe W. Ramos
Keyword(s):  
Cell Adhesion ◽  
Expression Cloning ◽  
Signaling Proteins

scholarly journals The Adapter Protein SLP-76 Mediates “Outside-In” Integrin Signaling and Function in T Cells

2009 ◽  
Vol 29 (20) ◽  
pp. 5578-5589 ◽  
Author(s):  
R. G. Baker ◽  
C. J. Hsu ◽  
D. Lee ◽  
M. S. Jordan ◽  
J. S. Maltzman ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
Sh2 Domain ◽  
Integrin Signaling ◽  
Signaling Proteins ◽  
Adapter Protein ◽  
Tcr Signaling ◽  
Integrin Ligands ◽  
And Function

ABSTRACT The adapter protein SH2 domain-containing leukocyte protein of 76 kDa (SLP-76) is an essential mediator of signaling from the T-cell antigen receptor (TCR). We report here that SLP-76 also mediates signaling downstream of integrins in T cells and that SLP-76-deficient T cells fail to support adhesion to integrin ligands. In response to both TCR and integrin stimulation, SLP-76 relocalizes to surface microclusters that colocalize with phosphorylated signaling proteins. Disruption of SLP-76 recruitment to the protein named LAT (linker for activation of T cells) inhibits SLP-76 clustering downstream of the TCR but not downstream of integrins. Conversely, an SLP-76 mutant unable to bind ADAP (adhesion and degranulation-promoting adapter protein) forms clusters following TCR but not integrin engagement and fails to support T-cell adhesion to integrin ligands. These findings demonstrate that SLP-76 relocalizes to integrin-initiated signaling complexes by a mechanism different from that employed during TCR signaling and that SLP-76 relocalization corresponds to SLP-76-dependent integrin function in T cells.

scholarly journals Regulation of nucleocytoplasmic trafficking by cell adhesion receptors and the cytoskeleton

2001 ◽  
Vol 155 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Andrew E. Aplin ◽  
R.L. Juliano
Keyword(s):  
Cell Adhesion ◽  
Growth Factors ◽  
Adhesion Molecule ◽  
Nuclear Import ◽  
Cell Adhesion Molecule ◽  
Signaling Cascades ◽  
Signaling Proteins ◽  
Nucleocytoplasmic Trafficking ◽  
Adhesion Receptors ◽  
Import And Export

It has become widely accepted that adhesion receptors can either directly activate, or significantly modulate, many of the signaling cascades initiated by circulating growth factors. An interesting recent development is the realization that adhesion receptors and their cytoskeletal partners can regulate the trafficking of signaling proteins between the cytoplasm and nucleus. Cell adhesion molecule control of nucleocytoplasmic trafficking allows adhesion to influence many cell decisions, and highlights the diversity of nuclear import and export mechanisms.

Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes

Cell ◽  
1989 ◽  
Vol 59 (6) ◽  
pp. 1203-1211 ◽  
Author(s):  
Laurelee Osborn ◽  
Catherine Hession ◽  
Richard Tizard ◽  
Cornelia Vassallo ◽  
Stefan Luhowskyj ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Expression Cloning ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1

scholarly journals The human E48 antigen, highly homologous to the murine Ly-6 antigen ThB, is a GPI-anchored molecule apparently involved in keratinocyte cell-cell adhesion.

1995 ◽  
Vol 129 (6) ◽  
pp. 1677-1689 ◽  
Author(s):  
R H Brakenhoff ◽  
M Gerretsen ◽  
E M Knippels ◽  
M van Dijk ◽  
H van Essen ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Core Protein ◽  
Sequence Similarity ◽  
Single Copy ◽  
Chromosome 8 ◽  
Expression Cloning ◽  
Target Antigen ◽  
Reading Frame ◽  
Antigen A ◽  
Cell Cell

The E48 antigen, a putative human homologue of the 20-kD protein present in desmosomal preparations of bovine muzzle, and formerly called desmoglein III (dg4), is a promising target antigen for antibody-based therapy of squamous cell carcinoma in man. To anticipate the effect of high antibody dose treatment, and to evaluate the possible biological involvement of the antigen in carcinogenesis, we set out to molecularly characterize the antigen. A cDNA clone encoding the E48 antigen was isolated by expression cloning in COS cells. Sequence analysis revealed that the clone contained an open reading frame of 128 amino acids, encoding a core protein of 13,286 kD. Database searching showed that the E48 antigen has a high level of sequence similarity with the mouse ThB antigen, a member of the Ly-6 antigen family. Phosphatidylinositol-specific (PI-specific) phospholipase-C treatment indicated that the E48 antigen is glycosylphosphatidylinositol-anchored (GPI-anchored) to the plasma membrane. The gene encoding the E48 antigen is a single copy gene, located on human chromosome 8 in the 8q24-qter region. The expression of the gene is confined to keratinocytes and squamous tumor cells. The putative mouse homologue, the ThB antigen, originally identified as an antigen on cells of the lymphocyte lineage, was shown to be highly expressed in squamous mouse epithelia. Moreover, the ThB expression level is in keratinocytes, in contrast to that in lymphocytes, not mouse strain related. Transfection of mouse SV40-polyoma transformed mouse NIH/3T3 cells with the E48 cDNA confirmed that the antigen is likely to be involved in cell-cell adhesion.

scholarly journals Antiparallel protocadherin homodimers use distinct affinity- and specificity-mediating regions in cadherin repeats 1-4

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
John M Nicoludis ◽  
Bennett E Vogt ◽  
Anna G Green ◽  
Charlotta PI Schärfe ◽  
Debora S Marks ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Neuronal Networks ◽  
Hydrophobic Interactions ◽  
Signaling Proteins ◽  
Sequence Comparisons ◽  
Loop Region ◽  
Coevolution Analysis ◽  
Polar Residues ◽  
Interaction Strategy ◽  
Specific Conservation

Protocadherins (Pcdhs) are cell adhesion and signaling proteins used by neurons to develop and maintain neuronal networks, relying on trans homophilic interactions between their extracellular cadherin (EC) repeat domains. We present the structure of the antiparallel EC1-4 homodimer of human PcdhγB3, a member of the γ subfamily of clustered Pcdhs. Structure and sequence comparisons of α, β, and γ clustered Pcdh isoforms illustrate that subfamilies encode specificity in distinct ways through diversification of loop region structure and composition in EC2 and EC3, which contains isoform-specific conservation of primarily polar residues. In contrast, the EC1/EC4 interface comprises hydrophobic interactions that provide non-selective dimerization affinity. Using sequence coevolution analysis, we found evidence for a similar antiparallel EC1-4 interaction in non-clustered Pcdh families. We thus deduce that the EC1-4 antiparallel homodimer is a general interaction strategy that evolved before the divergence of these distinct protocadherin families.

scholarly journals PSD-95 binding dynamically regulates NLGN1 trafficking and function

2019 ◽  
pp. 201821775 ◽  
Author(s):  
Jaehoon Jeong ◽  
Saurabh Pandey ◽  
Yan Li ◽  
John D. Badger ◽  
Wei Lu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Adhesion Molecules ◽  
Cell Adhesion Molecule ◽  
Surface Expression ◽  
Scaffolding Protein ◽  
Excitatory Synapses ◽  
Signaling Proteins ◽  
Synaptic Development ◽  
Synaptic Localization ◽  
And Function

PSD-95 is a scaffolding protein that regulates the synaptic localization of many receptors, channels, and signaling proteins. The NLGN gene family encodes single-pass transmembrane postsynaptic cell adhesion molecules that are important for synapse assembly and function. At excitatory synapses, NLGN1 mediates transsynaptic binding with neurexin, a presynaptic cell adhesion molecule, and also binds to PSD-95, although the relevance of the PSD-95 interaction is not clear. We now show that disruption of the NLGN1 and PSD-95 interaction decreases surface expression of NLGN1 in cultured neurons. Furthermore, PKA phosphorylates NLGN1 on S839, near the PDZ ligand, and dynamically regulates PSD-95 binding. A phosphomimetic mutation of NLGN1 S839 significantly reduced PSD-95 binding. Impaired NLGN1/PSD-95 binding diminished synaptic NLGN1 expression and NLGN1-mediated synaptic enhancement. Our results establish a phosphorylation-dependent molecular mechanism that regulates NLGN1 and PSD-95 binding and provides insights into excitatory synaptic development and function.

scholarly journals Antiparallel protocadherin homodimers use distinct affinity- and specificity-mediating regions in cadherin repeats 1-4

2016 ◽  
Author(s):  
John M. Nicoludis ◽  
Bennett E. Vogt ◽  
Anna G. Green ◽  
Charlotta P. I. Schärfe ◽  
Debora S. Marks ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Neuronal Networks ◽  
Hydrophobic Interactions ◽  
Signaling Proteins ◽  
Sequence Comparisons ◽  
Loop Region ◽  
Coevolution Analysis ◽  
Polar Residues ◽  
Interaction Strategy ◽  
Specific Conservation

ABSTRACTProtocadherins (Pcdhs) are cell adhesion and signaling proteins used by neurons to develop and maintain neuronal networks, relying on trans homophilic interactions between their extracellular cadherin (EC) repeat domains. We present the structure of the antiparallel EC1-4 homodimer of human PcdhYB3, a member of the γ subfamily of clustered Pcdhs. Structure and sequence comparisons of α, β, and γ clustered Pcdh isoforms illustrate that subfamilies encode specificity in distinct ways through diversification of loop region structure and composition in EC2 and EC3, which contains isoform-specific conservation of primarily polar residues. In contrast, the EC1/EC4 interface comprises hydrophobic interactions that provide non-selective dimerization affinity. Using sequence coevolution analysis, we found evidence for a similar antiparallel EC1-4 interaction in non-clustered Pcdh families. We thus deduce that the EC1-4 antiparallel homodimer is a general interaction strategy that evolved before the divergence of these distinct protocadherin families.

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