scholarly journals ErbB-1 and ErbB-2 Acquire Distinct Signaling Properties Dependent upon Their Dimerization Partner

1998 ◽  
Vol 18 (9) ◽  
pp. 5042-5051 ◽  
Author(s):  
Monilola A. Olayioye ◽  
Diana Graus-Porta ◽  
Roger R. Beerli ◽  
Jack Rohrer ◽  
Brigitte Gay ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Adaptor Protein ◽  
Receptor Activation ◽  
Erbb Receptors ◽  
Antibody Treatment ◽  
Receptor Phosphorylation ◽  
Biological Responses ◽  
Monoclonal Antibody Treatment ◽  
Src Homology 2 Domain ◽  
Phosphopeptide Mapping

ABSTRACT The different epidermal growth factor (EGF)-related peptides elicit a diverse array of biological responses as the result of their ability to activate distinct subsets of ErbB receptor dimers, leading to the recruitment of different intracellular signaling networks. To specifically examine dimerization-dependent modulation of receptor signaling, we constructed NIH 3T3 cell lines expressing ErbB-1 and ErbB-2 singly and in pairwise combinations with each other ErbB family member. This model system allowed the comparison of EGF-activated ErbB-1 with ErbB-1 activated by Neu differentiation factor (NDF)-induced heterodimerization with ErbB-4. In both cases, ErbB-1 coupled to the adaptor protein Shc, but only when activated by EGF was it able to interact with Grb2. Compared to the rapid internalization of EGF-activated ErbB-1, NDF-activated ErbB-1 showed delayed internalization characteristics. Furthermore, the p85 subunit of phosphatidylinositol kinase (PI3-K) associated with EGF-activated ErbB-1 in a biphasic manner, whereas association with ErbB-1 transactivated by ErbB-4 was monophasic. The signaling properties of ErbB-2 following heterodimerization with the other ErbB receptors or homodimerization induced by point mutation or monoclonal antibody treatment were also analyzed. ErbB-2 binding to peptides containing the Src homology 2 domain of Grb2 or p85 and the phosphotyrosine binding domain of Shc varied according to the mode of receptor activation. Finally, tryptic phosphopeptide mapping of both ErbB-1 and ErbB-2 revealed that receptor phosphorylation is dependent on the dimerization partner. Differential receptor phosphorylation may, therefore, be the basis for the differences in the signaling properties observed.

scholarly journals Positive Association of Human SHC3 Gene with Schizophrenia in a Northeast Chinese Han Population

2020 ◽  
Vol 17 (9) ◽  
pp. 934-940
Author(s):  
Ye Lv ◽  
Yang Sun ◽  
Guan-Yu Wang ◽  
Jian Yin ◽  
Cheng-Jie Li ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Susceptibility Gene ◽  
Adaptor Protein ◽  
Positive Association ◽  
Epidemiological Studies ◽  
Disease Genes ◽  
Chinese Han ◽  
Association Analyses ◽  
Independent Case ◽  
Src Homology 2 Domain

Objective Schizophrenia is one of the most devastating neuropsychiatric disorders. Genetic epidemiological studies have confirmed that schizophrenia is a genetic disease. Genes promoting neurodevelopment may be potential candidates for schizophrenia. As an adaptor linking a number of tyrosine kinase receptors in multiple intracellular signaling cascades, Src homology 2 domain containing transforming protein 3 (<i>SHC3</i>) is a member of the Shc-like adaptor protein family, and expressed predominantly in the mature neurons of the central nervous system (CNS). In the present study, we aimed to investigate the association of <i>SHC3</i> and schizophrenia.Methods An independent case-control association study was performed in a sample including 710 schizophrenia patients and 1314 healthy controls from a Northeast Chinese Han population.Results The allelic and genotypic association analyses showed that four SNPs in <i>SHC3</i> significantly associated with schizophrenia (rs2316280, rs4877041, rs944485 and rs7021743). The haplotype composing of these four SNPs also showed significantly individual and global association with schizophrenia.Conclusion Our present results suggest <i>SHC3</i> as a susceptibility gene for schizophrenia.

scholarly journals SARS-CoV-2 Sequence Characteristics of COVID-19 Persistence and Reinfection

2021 ◽  
Author(s):  
Manish C Choudhary ◽  
Charles R Crain ◽  
Xueting Qiu ◽  
William Hanage ◽  
Jonathan Z Li
Keyword(s):  
Persistent Infection ◽  
Viral Evolution ◽  
Phylogenetic Reconstruction ◽  
Geographic Region ◽  
Antibody Treatment ◽  
Viral Genomes ◽  
Monoclonal Antibody Treatment ◽  
Viral Sequences ◽  
Sequence Characteristics ◽  
Baseline Health

Abstract Background Both SARS-CoV-2 reinfection and persistent infection have been reported, but sequence characteristics in these scenarios have not been described. We assessed published cases of SARS-CoV-2 reinfection and persistence, characterizing the hallmarks of reinfecting sequences and the rate of viral evolution in persistent infection. Methods A systematic review of PubMed was conducted to identify cases of SARS-CoV-2 reinfection and persistence with available sequences. Nucleotide and amino acid changes in the reinfecting sequence were compared to both the initial and contemporaneous community variants. Time-measured phylogenetic reconstruction was performed to compare intra-host viral evolution in persistent SARS-CoV-2 to community-driven evolution. Results Twenty reinfection and nine persistent infection cases were identified. Reports of reinfection cases spanned a broad distribution of ages, baseline health status, reinfection severity, and occurred as early as 1.5 months or &gt;8 months after the initial infection. The reinfecting viral sequences had a median of 17.5 nucleotide changes with enrichment in the ORF8 and N genes. The number of changes did not differ by the severity of reinfection and reinfecting variants were similar to the contemporaneous sequences circulating in the community. Patients with persistent COVID-19 demonstrated more rapid accumulation of sequence changes than seen with community-driven evolution with continued evolution during convalescent plasma or monoclonal antibody treatment. Conclusions Reinfecting SARS-CoV-2 viral genomes largely mirror contemporaneous circulating sequences in that geographic region, while persistent COVID-19 has been largely described in immunosuppressed individuals and is associated with accelerated viral evolution.

scholarly journals Use of a Unique Mobile Medical Asset in COVID Monoclonal Antibody Treatment

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 990
Author(s):  
Herman Morchel ◽  
David Clark ◽  
Leighanne Buenvenida ◽  
Chinwe Ogedegbe
Keyword(s):  
Emergency Department ◽  
Monoclonal Antibody ◽  
Patient Care ◽  
Emergency Care ◽  
Environmental Changes ◽  
Physical Space ◽  
Antibody Treatment ◽  
Monoclonal Antibody Treatment ◽  
Mobile Satellite ◽  
Novel Coronavirus

The COVID-19 pandemic and the subsequent surge of patients presented to emergency departments has forever changed the paradigm of delivering emergency care. The highly infectious nature of the 2019 Novel Coronavirus, or COVID-19, mandated strict environmental changes, novel patient care, and flexible strategies to continue to deliver efficient emergency care while maintaining appropriate physical distancing between suspect and non-suspect COVID-19 patients. The engagement of a unique rapidly deployable Mobile Satellite Emergency Department (MSED) with scalable capability from prompt care to resuscitation level allowed the emergency care team to optimize patient care and throughput. The MSED was strategically located adjacent to the ambulance entrance. While initially deployed to increase Emergency Department surge capacity, the MSED was repurposed to cohort and treat COVID patients with the monoclonal antibody, Bamlanivimab, who were expected to be discharged after treatment. This allowed for more efficient use of Emergency Department resources, including physical space and staffing.

scholarly journals Targeting the Calmodulin-Regulated ErbB/Grb7 Signaling Axis in Cancer Therapy

2013 ◽  
Vol 16 (2) ◽  
pp. 177 ◽  
Author(s):  
Antonio Villalobo ◽  
Irene García-Palmero ◽  
Silviya R. Stateva ◽  
Karim Jellali
Keyword(s):  
Cancer Therapy ◽  
Growth Factor Receptor ◽  
Adaptor Protein ◽  
Short Review ◽  
Receptor Protein ◽  
Pharmacological Intervention ◽  
Erbb Receptors ◽  
Aberrant Expression ◽  
Signaling Mechanism ◽  
Downstream Signaling

Signal transduction pathways essential for the survival and viability of the cell and that frequently present aberrant expression or function in tumors are attractive targets for pharmacological intervention in human cancers. In this short review we will describe the regulation exerted by the calcium-receptor protein calmodulin (CaM) on signaling routes involving the family of ErbB receptors - highlighting the epidermal growth factor receptor (EGFR/ErbB1) and ErbB2 - and the adaptor protein Grb7, a downstream signaling component of these receptors. The signaling mechanism of the ErbB/Grb7 axis and the regulation exerted by CaM on this pathway will be described. We will present a brief overview of the current efforts to inhibit the hyperactivity of ErbB receptors and Grb7 in tumors. The currently available information on targeting the CaM-binding site of these signaling proteins will be analyzed, and the pros and cons of directly targeting CaM versus the CaM-binding domain of the ErbB receptors and Grb7 as potential anti-cancer therapy will be discussed. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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