scholarly journals Cloning, Chromosome Localization, Expression, and Characterization of an Src Homology 2 and Pleckstrin Homology Domain-containing Insulin Receptor Binding Protein hGrb10γ

1997 ◽  
Vol 272 (46) ◽  
pp. 29104-29112 ◽  
Author(s):  
Lily Q. Dong ◽  
Hongyan Du ◽  
Sarah G. Porter ◽  
Lee F. Kolakowski ◽  
Adrian V. Lee ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Receptor Binding ◽  
Binding Protein ◽  
Pleckstrin Homology Domain ◽  
Pleckstrin Homology ◽  
Chromosome Localization ◽  
Src Homology 2 ◽  
Src Homology ◽  
Receptor Binding Protein

scholarly journals Characterization of the δ2 Glutamate Receptor-binding Protein Delphilin

2006 ◽  
Vol 281 (35) ◽  
pp. 25577-25587 ◽  
Author(s):  
Keiko Matsuda ◽  
Shinji Matsuda ◽  
Clare M. Gladding ◽  
Michisuke Yuzaki
Keyword(s):  
Glutamate Receptor ◽  
Receptor Binding ◽  
Binding Protein ◽  
Receptor Binding Protein

scholarly journals SH2-Bα is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase

1998 ◽  
Vol 335 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Kei KOTANI ◽  
Peter WILDEN ◽  
Tahir S. PILLAY
Keyword(s):  
Growth Factor ◽  
Insulin Receptor ◽  
Receptor Binding ◽  
Binding Protein ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Activation Loop ◽  
Adapter Protein ◽  
Insulin Signalling Pathway ◽  
Receptor Binding Protein

We identified SH2-Bα as an insulin-receptor-binding protein based on interaction screening in yeast hybrid systems and co-precipitation in cells. SH2-Bα contains pleckstrin-homology (‘PH’) and Src homology 2 (SH2) domains and is closely related to APS (adapter protein with a PH domain and an SH2 domain) and lnk, adapter proteins first identified in lymphocytes. SH2-Bα is ubiquitously expressed and is present in rat epididymal adipose tissue, liver and skeletal muscle, physiological sites of insulin action. On SDS/PAGE, SH2-Bα migrates at a molecular mass of 98 kDa, although the predicted size of SH2-Bα is 79.6 kDa. Insulin causes an electrophoretic mobility shift. SH2-Bα can be immunoprecipitated using anti-(insulin receptor) antibody from insulin-stimulated cells. Anti-phosphotyrosine antibody or the growth factor receptor-binding protein 2 (Grb2) SH2 domain precipitate SH2-Bα after insulin stimulation, suggesting that SH2-Bα is tyrosine-phosphorylated and may be a substrate for the insulin receptor. The SH2-Bα SH2 domain did not interact with insulin-receptor substrate (IRS) proteins or epidermal-growth-factor receptor. Mutation of the juxtamembrane and C-terminus of the insulin receptor did not abolish the interaction with the SH2 domain. This was further confirmed using a panel of activation-loop single point mutants where mutation of Tyr1158, Tyr1162 and Tyr1163 abolished interaction. Thus SH2-Bα is a likely component in the insulin-signalling pathway and may function as an alternative signalling protein by interacting with the activation loop of the insulin-receptor cytoplasmic domain.

Placental expression of the insulin receptor binding protein GRB10: Relation to human fetoplacental growth and fetal gender

Placenta ◽  
2015 ◽  
Vol 36 (11) ◽  
pp. 1225-1230 ◽  
Author(s):  
A. Mukhopadhyay ◽  
G. Ravikumar ◽  
P. Dwarkanath ◽  
H. Meraaj ◽  
A. Thomas ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Receptor Binding ◽  
Binding Protein ◽  
Fetal Gender ◽  
Insulin Receptor Binding ◽  
Receptor Binding Protein

scholarly journals Receptor-Binding Protein of Lactococcus lactis Phages: Identification and Characterization of the Saccharide Receptor-Binding Site

2006 ◽  
Vol 188 (7) ◽  
pp. 2400-2410 ◽  
Author(s):  
Denise M. Tremblay ◽  
Mariella Tegoni ◽  
Silvia Spinelli ◽  
Valérie Campanacci ◽  
Stéphanie Blangy ◽  
...  
Keyword(s):  
Binding Site ◽  
Lactococcus Lactis ◽  
Receptor Binding ◽  
Binding Protein ◽  
Receptor Binding Site ◽  
Glycerol Molecule ◽  
Vh Domain ◽  
Interaction Surface ◽  
Receptor Binding Protein

ABSTRACT Phage p2, a member of the lactococcal 936 phage species, infects Lactococcus lactis strains by binding initially to specific carbohydrate receptors using its receptor-binding protein (RBP). The structures of p2 RBP, a homotrimeric protein composed of three domains, and of its complex with a neutralizing llama VH domain (VHH5) have been determined (S. Spinelli, A. Desmyter, C. T. Verrips, H. J. de Haard, S. Moineau, and C. Cambillau, Nat. Struct. Mol. Biol. 13:85-89, 2006). Here, we show that VHH5 was able to neutralize 12 of 50 lactococcal phages belonging to the 936 species. Moreover, escape phage mutants no longer neutralized by VHH5 were isolated from 11 of these phages. All of the mutations (but one) cluster in the RBP/VHH5 interaction surface that delineates the receptor-binding area. A glycerol molecule, observed in the 1.7-Å resolution structure of RBP, was found to bind tightly (Kd = 0.26 μM) in a crevice located in this area. Other saccharides bind RBP with comparable high affinity. These data prove the saccharidic nature of the bacterial receptor recognized by phage p2 and identify the position of its binding site in the RBP head domain.

scholarly journals Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2) domain (APS) and SH2-B enhance insulin-receptor autophosphorylation, extracellular-signal-regulated kinase and phosphoinositide 3-kinase-dependent signalling

2003 ◽  
Vol 371 (2) ◽  
pp. 405-412 ◽  
Author(s):  
Zamal AHMED ◽  
Tahir S. PILLAY
Keyword(s):  
Insulin Receptor ◽  
Chinese Hamster ◽  
Sh2 Domain ◽  
Adapter Protein ◽  
Pleckstrin Homology ◽  
Akt Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Src Homology 2 ◽  
Extracellular Signal ◽  
Src Homology

Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2) domain (APS) and SH2-B are adapter proteins and substrates that interact with the activation loop of the insulin-receptor (IR) kinase. These proteins are homologous and share substantial sequence similarity. We previously showed [Ahmed, Smith and Pillay, FEBS Lett. 475, 31–34], for the first time, that insulin-stimulated phosphorylation of APS led to interaction with c-Cbl in 3T3-L1 adipocytes and in transfected Chinese-hamster ovary (CHO) cells. In the present study, we find that insulin stimulates the membrane translocation and phosphorylation of APS to a much greater extent than SH2-B, despite the structural similarity of these proteins. Expression of APS or SH2-B delays IR tyrosine and IR substrate (IRS) dephosphorylation. This enhancement of signalling is also observed downsteam of the receptor. In control cells that lack APS, following insulin stimulation, extracellular-signal-regulated kinase (ERK) and Akt kinase reach maximal activation and then decline to basal levels by 60min. In contrast, in APS- and SH2-B-expressing cells, ERK and Akt kinase activation remains at peak levels at 60min. These effects may occur because these proteins either stabilize the active conformation or prevent dephosphorylation of the IR. We therefore conclude that, despite the ability to couple to c-Cbl, APS functions as a positive regulator of IR signalling and, although SH2-B is a poor substrate for the IR, its association with the IR allows it to regulate pathways downstream of the receptor independently of its phosphorylation.

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