title: NOK/STYK1 has a strong tendency towards forming aggregates and colocalises with epidermal growth factor receptor in endosomes.
abstract: Our previous studies showed that the overexpression of Novel Oncogene with Kinase-domain (NOK)/STYK1 led to cellular transformation, tumorigenesis and metastasis. This report characterises the subcellular distribution of NOK in HeLa cells and its localisation in early endosomes. Confocal immunolocalisation studies indicated that NOK had structural subtypes and was distributed into two distinct expression patterns: a dot pattern (DP) and an aggregation pattern (AP). The results of an immunohistochemistry (IHC) analysis of pathological tissues also showed that high expression level of endogenous NOK was expressed in an aggregate-like structure in vivo. Importantly, we found that NOK was localised in endosomes and colocalised with epidermal growth factor receptor (EGFR) in activated endosomal vesicles. However, as the stimulation time increased, NOK and EGFR began to progress through different pathways. EGFR was gradually degraded after treatment with EGF for approximately 20 min, whereas NOK levels were not reduced. This result suggests that NOK mainly plays a role in facilitating the trafficking of EGFR from early endosomes to later endosomes/lysosomes. Taken together, NOK has a strong tendency towards forming aggregates, which may have physiological implications and provide the first evidence that this novel receptor kinase is colocalised with EGFR in endosomes to participate in a post-internalisation step of EGFR.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Ding
authors.forename: Qing-Bo
authors.initials: QB
authors.lastname: Jiang
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Shaoyong
authors.initials: S
authors.lastname: Chen
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
mesh_terms: D002462:Cell Membrane / Q000201:enzymology; D011992:Endosomes / Q000201:enzymology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C482299:STYK1 protein, human