ArticleProceedings of the National Academy of Sciences of the United States of America2009
Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
204 citing papers in PubMed, 333 citations in OpenAlex.
- Modulating pseudokinase conformation from the ATP-binding site.Structure (London, England : 1993) · 2026Article
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- Structures of the PI3Kα/KRas complex on lipid bilayers reveal molecular mechanisms of PI3Kα activation.Molecular cell · 2026Article
- The multifaceted roles of receptor tyrosine pseudokinases in cellular signalling.Biochemical Society transactions · 2026Review
- ErbB family receptor dimerization dynamics and dysregulation via long-term single-molecule imaging.Cell · 2026Article
- Regulation of sebaceous gland homeostasis and sebum secretion by the ERBB receptor family.iScience · 2026Review
- Optogenetic Translocation to Subcellular Compartments through Regulation of Protein Avidity.ACS synthetic biology · 2026Article
- Pattern of HER2 and HER3 Overexpression in Patients with Pancreatic Ductal Adenocarcinoma.Medicina (Kaunas, Lithuania) · 2026Observational
- Signaling pathways and potential therapeutic agents in trastuzumab-induced cardiotoxicity.Apoptosis : an international journal on programmed cell death · 2026Review
- HER3-targeting Antibody-drug Conjugates Therapy for Solid Tumors: Recent Advances and Future Potentials.Current medicinal chemistry · 2026Review
- Structural and evolutionary insights into understudied bacterial serine-threonine pseudokinase families.Biochemical Society transactions · 2025Review
- Novel Humanized Anti-HER3 Antibodies: Structural Characterization and Therapeutic Activity.Antibodies (Basel, Switzerland) · 2025Article
- HER3: Unmasking a twist in the tale of a previously unsuccessful therapeutic pursuit targeting a key cancer survival pathway.Genes & diseases · 2025Review
- Current understanding of PEAK family members in regulation of cellular signaling pathways and cancer therapy.Molecular and cellular biochemistry · 2025Review
- Emerging importance of HER3 in tumorigenesis and cancer therapy.Nature reviews. Clinical oncology · 2025Review
- Identification of EcpK, a bacterial tyrosine pseudokinase important for exopolysaccharide biosynthesis inJournal of bacteriology · 2025Article
- Diverse ERBB2/ERBB3 Activating Alterations and Coalterations Have Implications for HER2/3-Targeted Therapies across Solid Tumors.Cancer research communications · 2025Article
- Signaling pathway dysregulation in breast cancer.Oncotarget · 2025Review
- The Therapeutic Significance of HER3 in Non-small Cell Lung Cancer (NSCLC): A Review Study.Current medicinal chemistry · 2025Review
- Effectiveness of afatinib after long-term gefitinib treatment forRespiratory medicine case reports · 2025Article
144 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
The kinase domain of human epidermal growth factor receptor (HER) 3/ErbB3, a member of the EGF receptor (EGFR) family, lacks several residues that are critical for catalysis. Because catalytic activity in EGFR family members is switched on by an allosteric interaction between kinase domains in an asymmetric kinase domain dimer, HER3 might be specialized to serve as an activator of other EGFR family members. We have determined the crystal structure of the HER3 kinase domain and show that it appears to be locked into an inactive conformation that resembles that of EGFR and HER4. Although the crystal structure shows that the HER3 kinase domain binds ATP, we confirm that it is catalytically inactive but can serve as an activator of the EGFR kinase domain. The HER3 kinase domain forms a dimer in the crystal, mediated by hydrophobic contacts between the N-terminal lobes of the kinase domains. This N-lobe dimer closely resembles a dimer formed by inactive HER4 kinase domains in crystal structures determined previously, and molecular dynamics simulations suggest that the HER3 and HER4 N-lobe dimers are stable. The kinase domains of HER3 and HER4 form similar chains in their respective crystal lattices, in which N-lobe dimers are linked together by reciprocal exchange of C-terminal tails. The conservation of this tiling pattern in HER3 and HER4, which is the closest evolutionary homolog of HER3, might represent a general mechanism by which this branch of the HER receptors restricts ligand-independent formation of active heterodimers with other members of the EGFR family.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.