Nakamura T , Nakamura T , Matsumoto K .

	1. Schematic structures of kringle domain and Krm.(A) The kringle domain and localization of a variable/unique stretch of 5 or 6 amino acids (blue circles) surrounded by two highly conserved sequences (yellow circles).(B) Multiple alignments of amino acid sequences of two highly conserved sequences that surround a variable region of the kringle domain. Two highly conserved sequences are boxed with yellow. (C) Outline for comprehensive analysis of partial cDNA fragments for kringle-containing proteins. PCR-amplified kringle tags are concatenated and ligated into the cloning plasmid. For details, see Nakamura et al.[3].(D) Schematic representation of the two transmembrane proteins containing kringle domain, Krm and Ror.
	2. Regulation of Wnt/-catenin signalling pathway.(A) Wnt forms a ternary complex with Fz and Lrp5/6, which promotes stabilization of β-catenin, thereby activating the pathway. (B) Dkk1 forms a ternary complex with Lrp5/6 and Krm, which blocks Wnt signal transduction by causing endocytosis of Lrp5/6. (C) Ror is the receptor for Wnt5a and blocks Wnt/-catenin signalling by inhibiting β-catenin-dependent gene transcription. (D) WIF and sFRP antagonize the binding of Wnt to Fz.
	3. Spatial expression patterns of krm1 mRNA in mouse embryo. (A–C) In situ hybridization of E10.5 mouse whole embryo. Lateral (A), dorsal (B) and ventral (C) view of embryo.(D) Schematic representation of E12.5 and E13.5 mouse embryos. Lines indicate the level of the sections shown in E–H, respectively. (E–H) In situ hybridization of E12.5 and E13.5 mouse transverse sections. E–H show the rostral and the lumbar level sections of E12.5 mouse embryo and the rostral and the lumbar level sections of E13.5 mouse embryo, respectively. AER, apical ectodermal ridge;fl, forelimb bud; h, heart; hl, hindlimb bud; l, lung;np, nasal pit;op, optic vesicle; ot, otic vesicle;fp, floor plate.
	4. (A) Expressions of krm1 mRNA in whole mouse embryos at serial developmental stages.(B) Tissue distribution of krm1 mRNA in adult mouse.(C) Change in the expression of krm1 mRNA during myogenic differentiation in C2C12 cells. Expression of krm1 mRNA in C2C12 cells cultured for various periods under conditions permissive for differentiation was analysed.(D) Expressions of krm1 mRNA in human cancer cell lines.
	5. Putative model involved in constitutively active Wnt/β-catenin signalling in cancer cells, from the aspect of decreased or diminished Krm expression. In normal cells, cytoplasmic β-catenin level is bi-directionally regulated by the complex formations between Lrp5/6-Wnt-Fz and Lrp5/6-Dkk-Krm. In contrast, in cancer cells, the decreased or diminished expression of Krm allows constitutive accumulation of β-catenin, leading to abnormal Wnt/β-catenin signalling.

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