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J Biol Chem. 2017 Nov 10;292(45):18565-18576. doi: 10.1074/jbc.M117.800771. Epub 2017 Sep 27.

Surfactant protein A down-regulates epidermal growth factor receptor by mechanisms different from those of surfactant protein D.

Author information

1
From the Departments of Biochemistry, y-hasegawa@sapmed.ac.jp.
2
Respiratory Medicine and Allergology, and.
3
From the Departments of Biochemistry.
4
Molecular Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060 8556, Japan.

Abstract

We recently reported that the lectin surfactant protein D (SP-D) suppresses epidermal growth factor receptor (EGFR) signaling by interfering with ligand binding to EGFR through an interaction between the carbohydrate-recognition domain (CRD) of SP-D and N-glycans of EGFR. Here, we report that surfactant protein A (SP-A) also suppresses EGF signaling in A549 human lung adenocarcinoma cells and in CHOK1 cells stably expressing human EGFR and that SP-A inhibits the proliferation and motility of the A549 cells. Results with 125I-EGF indicated that SP-A interferes with EGF binding to EGFR, and a ligand blot analysis suggested that SP-A binds EGFR in A549 cells. We also found that SP-A directly binds the recombinant extracellular domain of EGFR (soluble EGFR or sEGFR), and this binding, unlike that of SP-D, was not blocked by EDTA, excess mannose, or peptide:N-glycosidase F treatment. We prepared a collagenase-resistant fragment (CRF) of SP-A, consisting of CRD plus the neck domain of SP-A, and observed that CRF directly binds sEGFR but does not suppress EGF-induced phosphorylation of EGFR in or proliferation of A549 cells. These results indicated that SP-A binds EGFR and down-regulates EGF signaling by inhibiting ligand binding to EGFR as well as SP-D. However, unlike for SP-D, SP-A lectin activity and EGFR N-glycans were not involved in the interaction between SP-A and EGFR. Furthermore, our results suggested that oligomerization of SP-A is necessary to suppress the effects of SP-A on EGF signaling.

KEYWORDS:

collectin; epidermal growth factor receptor (EGFR); lung cancer; oligomerization; pulmonary surfactant

PMID:
28972165
PMCID:
PMC5682966
DOI:
10.1074/jbc.M117.800771
[Indexed for MEDLINE]
Free PMC Article

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