Nanoparticle-mediated activation of receptor signaling (WP2643)

Homo sapiens

Nanoparticle-mediated activation of receptor signaling. Several NP formulations were shown to interact with cellular receptors such as the EGFR and integrins, inducing cellular phenotypes such as proliferation, apoptosis, differentiation, and migration. In lung epithelial cells, NPs interact with both EGFR and integrins, leading to cell proliferation via activation of PI3K and AKT. NPs were shown to activate the EGFR, leading in parallel to apoptosis and proliferation, and oncogenic Ras mutations might influence these effects. Interestingly, while integrin-mediated activation of ERK was instrumental for proliferation, apoptosis was mediated via activation of JNK. In addition, NPs (PM2.5) are able to bind the EGFR to activate the MAPK signaling cascade. Activation of ERK leads to the expression and secretion of the epidermal growth factor amphiregulin, thus forming an autocrine loop, which might be instrumental for sustained inflammatory responses. Nanoparticles are depicted as red circles. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


Bart Smeets , Elisa Cirillo , Egon Willighagen , Kristina Hanspers , and Laurent Winckers


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Homo sapiens


Adverse Outcome Pathways Nanomaterials Pathways


Pathway Ontology

signaling pathway nanomaterial response pathway


Label Type Compact URI Comment
ROS Metabolite wikidata:Q424361
ROS Metabolite wikidata:Q424361
Fibronectin Protein uniprot:P02751
Amphiregulin Protein uniprot:P15514
Collagen Protein uniprot:P02452
α Protein uniprot:P56199
HRAS Protein uniprot:P01112
EGFR Protein uniprot:P00533
NRAS Protein uniprot:P01111
KRAS Protein uniprot:P01116
RAF Protein uniprot:P04049
MAP2K1 Protein uniprot:Q02750
MAP2K2 Protein uniprot:P36507
MAPK1 Protein uniprot:P28482
JNK1 Protein uniprot:P45983
JNK2 Protein uniprot:P45984
JNK3 Protein uniprot:P53779
MAPK12 Protein uniprot:P53778
MAPK13 Protein uniprot:O15264
MAPK14 Protein uniprot:Q16539
MAPK11 Protein uniprot:Q15759
β Protein uniprot:P05556
Talin Protein uniprot:Q9Y490
Paxillin Protein uniprot:P49023
Src Protein uniprot:P12931
FAK Protein uniprot:Q05397
Sos Protein uniprot:Q07889
Grb Protein uniprot:P62993
PI3K Protein uniprot:O00329
AKT Protein uniprot:Q9Y243


  1. Big signals from small particles: regulation of cell signaling pathways by nanoparticles. Rauch J, Kolch W, Laurent S, Mahmoudi M. Chem Rev. 2013 May 8;113(5):3391–406. PubMed Europe PMC Scholia