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

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.

• Authors: Yoshihiro Hasegawa, Motoko Takahashi, Shigeru Ariki, Atsushi Saito, Yasuaki Uehara, Rina Takamiya, Koji Kuronuma, Hirofumi Chiba, Yuji Sakuma, Hiroki Takahashi, Yoshio Kuroki
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 292 Issue 45 Pg. 18565-18576 (11 10 2017) ISSN: 1083-351X [Electronic] United States
• PMID: 28972165 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Ligands
• Peptide Fragments
• Pulmonary Surfactant-Associated Protein A
• Pulmonary Surfactant-Associated Protein D
• Recombinant Fusion Proteins
• Recombinant Proteins
• Epidermal Growth Factor
• EGFR protein, human
• ErbB Receptors

Topics

• A549 Cells
• Animals
• CHO Cells
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Cricetulus
• Epidermal Growth Factor (antagonists & inhibitors, genetics, metabolism)
• ErbB Receptors (agonists, antagonists & inhibitors, genetics, metabolism)
• Humans
• Ligands
• Peptide Fragments (chemistry, genetics, metabolism)
• Phosphorylation
• Protein Interaction Domains and Motifs
• Protein Interaction Mapping
• Protein Processing, Post-Translational
• Pulmonary Alveoli (metabolism)
• Pulmonary Surfactant-Associated Protein A (genetics, metabolism)
• Pulmonary Surfactant-Associated Protein D (genetics, metabolism)
• Recombinant Fusion Proteins (chemistry, metabolism)
• Recombinant Proteins (chemistry, metabolism)
• Signal Transduction