scholarly journals Activation of p38α/β MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo

2006 ◽  
Vol 175 (3) ◽  
pp. 383-388 ◽  
Author(s):  
Giichi Takaesu ◽  
Jong-Sun Kang ◽  
Gyu-Un Bae ◽  
Min-Jeong Yi ◽  
Clement M. Lee ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cell Surface ◽  
Mapk Pathway ◽  
Surface Protein ◽  
Scaffold Protein ◽  
Mitogen Activated Protein Kinase ◽  
Cell Surface Receptor ◽  
Immunoglobulin Superfamily ◽  
Surface Complexes ◽  
Primary Myoblasts

The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cell differentiation, but the signaling mechanisms by which it is activated during this process are largely unknown. Cdo is an immunoglobulin superfamily member that functions as a component of multiprotein cell surface complexes to promote myogenesis. In this study, we report that the Cdo intracellular region interacts with JLP, a scaffold protein for the p38α/β MAPK pathway. Cdo, JLP, and p38α/β form complexes in differentiating myoblasts, and Cdo and JLP cooperate to enhance levels of active p38α/β in transfectants. Primary myoblasts from Cdo−/− mice, which display a defective differentiation program, are deficient in p38α/β activity, and the expression of an activated form of MKK6 (an immediate upstream activator of p38) rescues the ability of Cdo−/− cells to differentiate. These results document a novel mechanism of signaling during cell differentiation: the interaction of a MAPK scaffold protein with a cell surface receptor.

scholarly journals A Cdo–Bnip-2–Cdc42 signaling pathway regulates p38α/β MAPK activity and myogenic differentiation

2008 ◽  
Vol 182 (3) ◽  
pp. 497-507 ◽  
Author(s):  
Jong-Sun Kang ◽  
Gyu-Un Bae ◽  
Min-Jeong Yi ◽  
Youn-Joo Yang ◽  
Ji-Eun Oh ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Cell Surface ◽  
Mapk Pathway ◽  
Myogenic Differentiation ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Cell Surface Receptor ◽  
Myoblast Differentiation ◽  
Loss Of Function ◽  
Surface Receptor

The p38α/β mitogen-activated protein kinase (MAPK) pathway promotes skeletal myogenesis, but the mechanisms by which it is activated during this process are unclear. During myoblast differentiation, the promyogenic cell surface receptor Cdo binds to the p38α/β pathway scaffold protein JLP and, via JLP, p38α/β itself. We report that Cdo also interacts with Bnip-2, a protein that binds the small guanosine triphosphatase (GTPase) Cdc42 and a negative regulator of Cdc42, Cdc42 GTPase-activating protein (GAP). Moreover, Bnip-2 and JLP are brought together through mutual interaction with Cdo. Gain- and loss-of-function experiments with myoblasts indicate that the Cdo–Bnip-2 interaction stimulates Cdc42 activity, which in turn promotes p38α/β activity and cell differentiation. These results reveal a previously unknown linkage between a cell surface receptor and downstream modulation of Cdc42 activity. Furthermore, interaction with multiple scaffold-type proteins is a distinctive mode of cell surface receptor signaling and provides one mechanism for specificity of p38α/β activation during cell differentiation.

scholarly journals Thyroid hormone stimulation of extracellular signal-regulated kinase and cell proliferation in human osteoblast-like cells is initiated at integrin αVβ3

2008 ◽  
Vol 196 (3) ◽  
pp. 509-517 ◽  
Author(s):  
A Scarlett ◽  
M P Parsons ◽  
P L Hanson ◽  
K K Sidhu ◽  
T P Milligan ◽  
...  
Keyword(s):  
Cell Surface ◽  
Thymidine Incorporation ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cell Surface Receptor ◽  
Human Osteoblast ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Surface Receptor

The aim of the present study was to examine whether triiodo-l-thyronine (T3) or l-thyroxine (T4) rapidly activated the mitogen-activated protein kinase (MAPK) intracellular signalling cascade in osteoblast-like cells and investigate whether this activation was initiated at the integrin αVβ3 cell surface receptor. Using PCR and western blotting, the expression of integrin αVβ3 mRNA and protein was demonstrated in the human osteoblast-like cell lines MG-63 and SaOS-2. The treatment of MG-63 cells with T3 (10 nM) or T4 (100 nM) for 10 min stimulated extracellular signal-regulated kinase activity (ERK, a component of the MAPK pathway) as determined by fluorescent immunocytochemistry and an immunocomplex activity assay (T3 by 10.7-fold, P<0.01 and T4 by 10.4-fold, P<0.01 compared with control). T3 (10 nM) and T4 (100 nM) also significantly stimulated thymidine incorporation into MG-63 cells by 2.3±0.7-fold (P<0.01) and 2.1±0.1-fold (P<0.05) respectively. To establish whether transient ERK activation via the integrin αVβ3 cell surface receptor mediated these effects, MG-63 cells were pretreated for 30 min with the specific MAPK kinase inhibitor, U0126 (1 μM), or an anti-integrin αVβ3-blocking antibody. Both pretreatments significantly inhibited T3- and T4-stimulated ERK activation and abolished T3-stimulated thymidine incorporation (P<0.01). T4-stimulated incorporation was significantly inhibited from 2.1- to 1.3-fold above control (P<0.05). Thus, our results suggest that T3 and T4 rapidly stimulate ERK activation in MG-63 cells via integrin αVβ3 and that one functional effect of this ERK activation is increased DNA synthesis.

scholarly journals Cdo Binds Abl To Promote p38α/β Mitogen-Activated Protein Kinase Activity and Myogenic Differentiation

2009 ◽  
Vol 29 (15) ◽  
pp. 4130-4143 ◽  
Author(s):  
Gyu-Un Bae ◽  
Bok-Geon Kim ◽  
Hye-Jin Lee ◽  
Ji-Eun Oh ◽  
Su-Jae Lee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Kinase Activity ◽  
Mapk Pathway ◽  
Myogenic Differentiation ◽  
Mitogen Activated Protein Kinase ◽  
Cell Surface Receptor ◽  
Myoblast Differentiation ◽  
Protein Kinase Activity ◽  
Mitogen Activated Protein

ABSTRACT The p38 mitogen-activated protein kinase (MAPK) pathway is required for differentiation of skeletal myoblasts, but how the pathway is activated during this process is not well understood. One mechanism involves the cell surface receptor Cdo (also known as Cdon), which binds to Bnip-2 and JLP, scaffold proteins for Cdc42 and p38, respectively; formation of these complexes results in Bnip-2/Cdc42-dependent activation of p38. It has been reported that the tyrosine kinase Abl promotes myogenic differentiation in a manner dependent on its cytoplasmic localization, but the cytoplasmic signaling proteins with which it interacts to achieve this effect are unidentified. We report that Abl associates with both Cdo and JLP during myoblast differentiation. Abl binds a proline-rich motif in Cdo via its SH3 domain, and these regions of Abl and Cdo are required for their promyogenic effects. Cdo is important for full Abl kinase activity, and Abl is necessary for full activation of p38 MAPK, during myogenic differentiation. As seen with myoblasts depleted of Cdo, the diminished differentiation displayed by Abl-depleted cells is rescued by the expression of an activated form of the immediate upstream p38-activating kinase MAPK kinase 6. Abl's promyogenic effect is therefore linked to a multiprotein cell surface complex that regulates differentiation-dependent p38 activation.

Immunogold and immunoblot studies on a cell surface protein found in primary mesenchyme cells and in the cortical secretory vesicles of the sea urchin egg

1987 ◽  
Vol 45 ◽  
pp. 832-833
Author(s):  
G.L. Decker ◽  
M.C. Valdizan
Keyword(s):  
Cell Surface ◽  
Sea Urchin ◽  
Surface Protein ◽  
Egg Cell ◽  
Secretory Vesicles ◽  
Cell Surface Protein ◽  
Surface Complexes ◽  
Mesenchyme Cells ◽  
Lowicryl K4m ◽  
Primary Mesenchyme Cells

A monoclonal antibody designated MAb 1223 has been used to show that primary mesenchyme cells of the sea urchin embryo express a 130-kDa cell surface protein that may be directly involved in Ca2+ uptake required for growth of skeletal spicules. Other studies from this laboratory have shown that the 1223 antigen, although in relatively low abundance, is also expressed on the cell surfaces of unfertilized eggs and on the majority of blastomeres formed prior to differentiation of the primary mesenchyme cells.We have studied the distribution of 1223 antigen in S. purpuratus eggs and embryos and in isolated egg cell surface complexes that contain the cortical secretory vesicles. Specimens were fixed in 1.0% paraformaldehyde and 1.0% glutaraldehyde and embedded in Lowicryl K4M as previously reported. Colloidal gold (8nm diameter) was prepared by the method of Mulpfordt.

scholarly journals Characterization of a cDNA encoding a cysteine-rich cell surface protein located in the flagellar pocket of the protozoan Trypanosoma brucei.

1990 ◽  
Vol 10 (9) ◽  
pp. 4506-4517 ◽  
Author(s):  
M G Lee ◽  
B E Bihain ◽  
D G Russell ◽  
R J Deckelbaum ◽  
L H Van der Ploeg
Keyword(s):  
Amino Acid ◽  
Cell Surface ◽  
Trypanosoma Brucei ◽  
Transmembrane Domain ◽  
Density Lipoprotein ◽  
Surface Protein ◽  
Integral Membrane Protein ◽  
Cell Surface Receptor ◽  
Flagellar Pocket ◽  
Cytoplasmic Extension

We have characterized a cDNA encoding a cysteine-rich, acidic integral membrane protein (CRAM) of the parasitic protozoa Trypanosoma brucei and Trypanosoma equiperdum. Unlike other membrane proteins of T. brucei, which are distributed throughout the cell surface, CRAM is concentrated in the flagellar pocket, an invagination of the cell surface of the trypanosome where endocytosis has been documented. Accordingly, CRAM also locates to vesicles located underneath the pocket, providing evidence of its internalization. CRAM has a predicted molecular mass of 130 kilodaltons and has a signal peptide, a transmembrane domain, and a 41-amino-acid cytoplasmic extension. A characteristic feature of CRAM is a large extracellular domain with a roughly 66-fold acidic, cysteine-rich 12-amino-acid repeat. CRAM is conserved among different protozoan species, including Trypanosoma cruzi, and CRAM has structural similarities with eucaryotic cell surface receptors. The most striking homology of CRAM is to the human low-density-lipoprotein receptor. We propose that CRAM functions as a cell surface receptor of different trypanosome species.

scholarly journals Divergent Traits and Ligand-Binding Features of the Cytomegalovirus CD48 Gene Family

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 23
Author(s):  
Pablo Martinez-Vicente ◽  
Domènec Farré ◽  
Elena Gracia-Latorre ◽  
Pablo Engel ◽  
Ana Angulo
Keyword(s):  
Cell Surface ◽  
Nk Cell ◽  
Viral Evolution ◽  
Costimulatory Molecule ◽  
Surface Protein ◽  
Gene Families ◽  
Biochemical Properties ◽  
Cell Surface Receptor ◽  
Type I ◽  
Independent Functions

The genesis of gene families through the capture of host genes and their subsequent duplication is a crucial process in the evolution of large DNA viruses. CD48 is a cell surface protein with an ectodomain composed of two immunoglobulin (Ig) domains. Via its N-terminal Ig domain, CD48 interacts with the cell surface receptor 2B4, triggering signal transduction events that regulate leukocyte cytotoxicity. We previously reported the presence of five CD48 homologs (vCD48s) in two related cytomegaloviruses, derived from a common host CD48 ancestor gene acquired by retrotranscription. Recently, we examined one member of this family, A43, showing that it acts as a functional viral decoy receptor, binding with high affinity and stability to 2B4 and impairing NK-cell cytotoxicity. Here, we have characterized the rest of the vCD48s. We show that they are highly glycosylated type I transmembrane proteins that display remarkably distinct features: dissimilar structures (e.g., different size stalks and cytoplasmic tails), biochemical properties, locations (cell surface/soluble), and temporal kinetic classes. We found that, in contrast to A43, none of them interacts with 2B4. Consistent with this, the molecular modeling of the N-terminal Ig domains of these vCD48s evidences significant changes in the numbers and lengths of their β-strands and inter-sheet loops that participate in the interaction of CD48 with 2B4. This suggests that these vCD48s have diverged to perform new 2B4-independent functions. Interestingly, we determined that one of them, S30, tightly binds CD2, a T- and NK-cell adhesion and costimulatory molecule whose primary ligand is CD58. Thus, altogether, our results show how a key host immune receptor captured by a virus can be subsequently remodeled during viral evolution to yield new molecules with improved affinities to their cognate receptors or with shifted binding specificities to additional immune targets, expanding the repertoire of viral immunoevasins.

scholarly journals Elevated Oral and Systemic Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Periodontitis

2012 ◽  
Vol 92 (2) ◽  
pp. 161-165 ◽  
Author(s):  
N. Bostanci ◽  
V.Ö. Öztürk ◽  
G. Emingil ◽  
G.N. Belibasakis
Keyword(s):  
Inflammatory Response ◽  
Cell Surface ◽  
Myeloid Cells ◽  
Aggressive Periodontitis ◽  
Cell Surface Receptor ◽  
Immunoglobulin Superfamily ◽  
Control Group ◽  
Inflammatory Biomarker ◽  
Surface Receptor ◽  
A Cell

The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell-surface receptor of the immunoglobulin superfamily, involved in the propagation of the inflammatory response to bacterial challenge. Soluble (s)TREM-1 is released from the cell surface during the course of infection and is a useful inflammatory biomarker in the early diagnosis of systemic sepsis. The hypothesis of this study was that oral and systemic levels of sTREM-1 are elevated in periodontitis. Therefore, the aim was to investigate, by ELISA, the sTREM-1 concentrations in saliva and serum of individuals without periodontitis (control) and persons with chronic or generalized aggressive periodontitis. In saliva, sTREM-1 concentrations were higher in chronic and aggressive periodontitis than in the control group, by 3.3-fold and 5.6-fold, respectively. In serum, these differences were 1.7-fold and 2-fold, respectively. However, there were no significant differences between the two forms of periodontitis, neither in saliva nor in serum. Salivary and serum sTREM-1 levels positively correlated with full-mouth clinical periodontal parameters. In conclusion, the increased oral and systemic levels of sTREM-1 in periodontitis denote a value for this molecule as a biomarker for the disease and may also have implications in the association between periodontal infections and systemic inflammatory response.

scholarly journals SUN-LB130 Identification of IGSF1 Ligands

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Courtney L Smith ◽  
Andrew N Bayne ◽  
Jean-François Trempe ◽  
Daniel J Bernard
Keyword(s):  
Cell Surface ◽  
Transmembrane Domain ◽  
Protein Complexes ◽  
Protein A ◽  
Negative Control ◽  
Cell Surface Receptor ◽  
Immunoglobulin Superfamily ◽  
Central Hypothyroidism ◽  
Surface Receptors ◽  
Surface Receptor

Abstract Immunoglobulin superfamily, member 1 (IGSF1), is an X-linked, type 1 transmembrane glycoprotein that is highly expressed in the anterior pituitary gland and testes. Mutations in the IGSF1 gene cause congenital central hypothyroidism, variable hypoprolactinemia, growth hormone dysregulation, and macroorchidism. Igsf1 knockout mice exhibit reduced pituitary TRH receptor (Trhr1) expression with an associated impairment in TRH-stimulated TSH secretion. The mechanism through which IGSF1 loss leads to reductions in Trhr1 levels is unresolved, at least in part because IGSF1’s cellular functions are unknown. The mature form of the IGSF1 protein consists of seven extracellular Ig loops, a single transmembrane domain containing a positively charged arginine, and a short intracellular carboxy-tail devoid of known functional motifs. Recently, IGSF1 was argued to be a member of the leukocyte receptor cluster (LRC) family. LRC proteins act as cell surface receptors for soluble or membrane-bound proteins. We therefore hypothesized that IGSF1 is a cell surface receptor for a presently undescribed ligand that regulates Trhr1 expression in pituitary thyrotrope cells. To identify candidate IGSF1 ligands, we implemented a new ligand trapping method, Ecto-Fc MS. We fused the extracellular (Ecto) domain of IGSF1 to the fragment crystallizable (Fc) region of human IgG, creating an Ecto-Fc fusion protein. Secreted IGSF1-Fc was purified and used as a ligand trap for bait proteins extracted from rat testes. The protein complexes were affinity purified with protein A beads, trypsin digested into peptides, subjected to orthogonal high-pH fractionation, and identified by tandem LC-MS/MS. More than 700 proteins were enriched in IGSF1-Fc preparations compared to an Fc-only negative control. Several secreted ligands and plasma-membrane proteins were identified, many of which are also expressed in pituitary thyrotrope cells. Identifying the ligand or ligands will enable us to determine IGSF1 function, and may lead to the discovery of novel causes of central hypothyroidism and macroorchidism.

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