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Functional characterization of lysophosphatidic acid receptor 1 mutants identified in rat cancer tissues.

Abstract：

:Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts various cellular effects through activation of LPA receptors, LPA1-LPA6, in many types of cells including cancer cells. We recently found several missense mutations of Lpar1 in rat cancer tissues. One of these mutations is located at the extracellular tip of the seventh transmembrane domain of LPA1, and another three mutations are found within the NPXXY motif in the seventh transmembrane domain. These mutants are designated F295S LPA1 and P308S, I310T, and Y311H LPA1, respectively. Here, we examined the functions of these LPA1 mutants. Compared with wild-type (WT) LPA1, F295S, P308S, and I310T LPA1 showed decreased maximal responses in inhibition of cAMP formation, Ca2+ mobilization, and cytoskeletal changes. Y311H LPA1 failed to show LPA-induced cellular responses. However, these LPA1 mutants were internalized in response to LPA exposure. Finally, while WT and F295S LPA1 showed a similar, broad distribution throughout the cell, P308S, I310T, and Y311H LPA1 displayed a restricted cellular distribution and co-localized with the endoplasmic reticulum. These data suggest that the LPA1 mutants perturb LPA signaling in cancer tissues.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Ishii S,Tsujiuchi T,Fukushima N

doi

10.1016/j.bbrc.2017.03.118

subject

Has Abstract

pub_date

2017-05-06 00:00:00

pages

767-773

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(17)30586-7

journal_volume

486

pub_type

杂志文章

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