The receptor tyrosine kinase Ror2 associates with the melanoma-associated antigen (MAGE) family protein Dlxin-1 and regulates its intracellular distribution

Takeru Matsuda, Hiroaki Suzuki, Isao Oishi, Shuichi Kani, Yoshikazu Kuroda, Takahide Komori, Aya Sasaki, Ken Watanabe, Yasuhiro Minami

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The mammalian Ror family receptor tyrosine kinases, Ror1 and Ror2, play crucial roles in developmental morphogenesis. Although the functions of Ror1 and Ror2 are redundant, Ror2 exhibits more specific functions during development. We show that when expressed in mammalian cells, Ror2, but not Ror1, associates with the melanoma-associated antigen (MAGE) family protein, Dlxin-1, which is known to bind to the homeodomain proteins Msx2 and Dlx5 and regulate their transcriptional functions. This association requires the cytoplasmic C-terminal region of Ror2, containing proline-rich and serine/threonine-rich domains, and the C-terminal necdin homology domain of Dlxin-1. Interestingly, the cytoplasmic C-terminal region of Ror2 is missing in patients with brachydactyly type B. Interestingly, transient expression and immunohistochemical analyses reveal that both Dlxin-1 and Msx2 are co-localized in the nuclei in the absence of Ror2. In the presence of Ror2, Dlxin-1 is colocalized with Ror2 at the membranous compartments and Msx2 is retained in the nuclei. It was also found that the majority of cellular Dlxin-1 is retained in the membrane fractions of wild-type but not Ror2-/- mouse embryonic fibroblasts. Furthermore, we show that transcriptional activity of Msx2, irrespective of Ror2 kinase activity, is regulated by ectopic expression of Ror2 using a reporter plasmid containing the WIP element. Thus, Ror2 sequesters Dlxin-1 in membranous compartments, thereby affecting the transcriptional function of Msx2.

Original languageEnglish
Pages (from-to)29057-29064
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number31
DOIs
Publication statusPublished - 2003 Aug 1
Externally publishedYes

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Melanoma-Specific Antigens
Homeodomain Proteins
Receptor Protein-Tyrosine Kinases
Threonine
Morphogenesis
Proline
Serine
Plasmids
Phosphotransferases
Fibroblasts
Antigens
Membranes
Proteins
Cells
Ectopic Gene Expression
Type B1 Brachydactyly
necdin

ASJC Scopus subject areas

  • Biochemistry

Cite this

The receptor tyrosine kinase Ror2 associates with the melanoma-associated antigen (MAGE) family protein Dlxin-1 and regulates its intracellular distribution. / Matsuda, Takeru; Suzuki, Hiroaki; Oishi, Isao; Kani, Shuichi; Kuroda, Yoshikazu; Komori, Takahide; Sasaki, Aya; Watanabe, Ken; Minami, Yasuhiro.

In: Journal of Biological Chemistry, Vol. 278, No. 31, 01.08.2003, p. 29057-29064.

Research output: Contribution to journalArticle

Matsuda, Takeru ; Suzuki, Hiroaki ; Oishi, Isao ; Kani, Shuichi ; Kuroda, Yoshikazu ; Komori, Takahide ; Sasaki, Aya ; Watanabe, Ken ; Minami, Yasuhiro. / The receptor tyrosine kinase Ror2 associates with the melanoma-associated antigen (MAGE) family protein Dlxin-1 and regulates its intracellular distribution. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 31. pp. 29057-29064.
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AU - Matsuda, Takeru

AU - Suzuki, Hiroaki

AU - Oishi, Isao

AU - Kani, Shuichi

AU - Kuroda, Yoshikazu

AU - Komori, Takahide

AU - Sasaki, Aya

AU - Watanabe, Ken

AU - Minami, Yasuhiro

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