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| ERBB2 | |
|---|---|
| Name | Erb-B2 receptor tyrosine kinase 2 |
| Other names | HER2, Neu |
| Organism | Human |
| Uniprot | P04626 |
| Chromosomal location | 17q12 |
ERBB2
ERBB2 is a human receptor tyrosine kinase in the ErbB family implicated in signal transduction, cell proliferation, and differentiation. It is central to studies by institutions such as National Institutes of Health, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Harvard University, and Massachusetts Institute of Technology, and has been a focus in landmark efforts like the War on Cancer and the development efforts at pharmaceutical companies including Genentech, Roche, and Novartis. Key historical milestones involve researchers from University of California, San Francisco, Yale University, and Johns Hopkins University who mapped its oncogenic role alongside discoveries related to oncogenes, growth factors, and early cancer genetics exemplified by work at Sloan Kettering Institute.
ERBB2 encodes a single-pass transmembrane protein with an extracellular ligand-binding-like domain, a transmembrane helix, and an intracellular tyrosine kinase domain, informed by structural studies from groups at European Molecular Biology Laboratory, Max Planck Society, and Stanford University. High-resolution crystallography and cryo-EM efforts by teams at Diamond Light Source, Brookhaven National Laboratory, and Rutherford Appleton Laboratory elucidated dimerization interfaces shared with family members studied by researchers at Columbia University and University of Cambridge. Functional partnerships include heterodimer formation with family members whose characterization involved labs at University of Tokyo, University of Texas MD Anderson Cancer Center, and University of Chicago, integrating pathways described in reports from American Association for Cancer Research conferences and textbooks used at University of Oxford.
The ERBB2 locus on chromosomal band 17q12 is regulated by copy-number variation, promoter elements, and transcriptional control studied at Cold Spring Harbor Laboratory, European Bioinformatics Institute, and Broad Institute. Clinical genomic projects such as The Cancer Genome Atlas and 1000 Genomes Project catalogued amplifications and mutations, while epigenetic regulation has been investigated by teams at Wistar Institute and Fred Hutchinson Cancer Center. Post-translational regulation through ubiquitination, phosphorylation, and endocytic trafficking has been clarified in work from University of California, San Diego, Scripps Research Institute, and University College London.
ERBB2 signaling has conserved roles in organogenesis and tissue homeostasis, with developmental genetics contributions from researchers at Max Planck Institute for Molecular Genetics, Karolinska Institute, and University of Freiburg. Functional studies in vertebrate models conducted at Salk Institute, University of Cambridge, and Weizmann Institute of Science demonstrated roles in cardiac morphogenesis, neural crest development, and epithelial differentiation, paralleling classical developmental biology work from Columbia University and Princeton University. Physiological studies related to lactation, mammary gland development, and wound healing linked to programs at University of Pennsylvania, Imperial College London, and Monash University.
Amplification and overexpression of ERBB2 are hallmark features in subsets of breast cancer, and are implicated in subsets of gastric cancer, ovarian cancer, lung cancer, and salivary gland carcinoma, with epidemiological cohorts assembled by SEER Program, European Organisation for Research and Treatment of Cancer, and National Cancer Institute. Foundational clinical-pathological correlations were made at Memorial Sloan Kettering Cancer Center, Mayo Clinic, and Cleveland Clinic. Somatic mutations and resistance mechanisms were characterized in studies affiliated with Dana-Farber Cancer Institute, Vanderbilt University Medical Center, and University of Michigan.
Diagnostic strategies including immunohistochemistry and fluorescence in situ hybridization were standardized through collaborations among College of American Pathologists, American Society of Clinical Oncology, and reference laboratories at Johns Hopkins Hospital. Targeted therapies began with monoclonal antibody development at Genentech and clinical trials coordinated by groups at National Comprehensive Cancer Network centers, leading to agents approved following regulatory review by Food and Drug Administration and European Medicines Agency. Therapeutics include monoclonal antibodies, antibody-drug conjugates, tyrosine kinase inhibitors, and combination regimens developed in partnerships involving AstraZeneca, Pfizer, Amgen, and academic trial networks such as Cooperative Oncology Group and EORTC.
Ongoing research engages model organisms and platforms used at Jackson Laboratory, European Molecular Biology Laboratory, Wellcome Trust Sanger Institute, and community resources like Addgene. Mouse models, transgenic lines, patient-derived xenografts, and organoids developed at Broad Institute, Hubrecht Institute, and Cold Spring Harbor Laboratory enable mechanistic and preclinical therapeutic studies. Emerging directions intersect with precision oncology consortia including PAM50 subtype research, computational efforts at Institute for Systems Biology, and translational pipelines supported by Cancer Research UK and private foundations such as the Bill & Melinda Gates Foundation.
Category:Human proteins Category:Receptor tyrosine kinases