Journal
CANCER RESEARCH
Volume 67, Issue 5, Pages 1935-1942Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-06-3023
Keywords
-
Categories
Ask authors/readers for more resources
ErbB2 and ErbB3, two members of the ErbB family, form a high-affinity heregulin coreceptor that elicits potent mitogenic and transforming signals, and clinical studies indicate that these receptors play an important role in tumor incidence and progression. To determine whether N-glycosylation is involved in the function of ErbB3, a series of human ErbB3 molecules devoid of N-glycans were prepared and transfected to Flp-In-CHO cells for stable expression. A cross-linking study showed that the Asn(418) to Gin mutant (N418Q) of ErbB3 underwent autudimerization without its ligand, heregulin. The wild-type or N418Q mutant of ErbB3 was next coexpressed with FrbB2 in Flp-In-CHO cells, and the effect of N-glycan on heterodimerization was examined. The N418Q mutant of ErbB3 was autodimerized with ErbB2 without ligand stimulation, and receptor tyrosine phosphorylation and subsequent extracellular signal-regulated kinase (ERK) and Akt phosphorylation were promoted in the absence of heregulin. A cell proliferation assay and a soft agar colony formation assay showed that the N418Q mutant of ErbB3 coexpressed with ErbB2 promoted cell proliferation and colony formation in soft agar in an ERK- and Akt-dependent manner. The mutation also promoted the growth of tumors in athymic mice when injected s.c. These findings suggest that the Asn(418)- linked N-glycan in ErbB3 plays an essential role in regulating receptor heterodimerization with ErbB2 and might have an effect on transforming activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available