N

P120 1ABC

P120 2ABC

P120ctn 4ABC

Figure 4. Diagrammatic representations of the multiple isoforms of p120 catenin. Cell-type-specific alternative splicing events result in multiple isoforms of p120 catenin. Four N-terminal ATG start sites generate p120 isoforms 1, 2, 3, and 4. p120 isoform 1 contains a putative coiled-coil domain (C-C), which is absent from isoforms 2-4. Additional alternative splicing generates p120 isoforms using alternative exons in the C-terminal region, exons A, B and C. Isoforms are designated p120ctn 1-4, depending on the N-terminal start site. The A, B, and/or C designations refer to the exons present in the p120 catenin isoform. If none of the C-terminal exons are present, the letter N (for none) is used in the nomenclature (e.g. p120ctn1N). PD, phosphorylation domain; NLS, Nuclear localization sequence.

Similar to the situation with p and y-catenin, increased levels of p120ctn in the cytoplasm may direct translocation of p120ctn to the nucleus where a downstream signaling cascade is initiated. Although the mechanism of nuclear translocation and the molecular basis for p120ctn isoform specificity has not been described, post-translational modification of p120ctn may be one means of directing p120ctn into either the cytoplasmic or the nuclear compartments. Specific sites of Src-initiated phosphorylation have been identified in murine p120, isoform 1A (Mariner et al., 2001). All of the Src-stimulated phosphorylation sites are present in the amino terminus of p120ctn, whereas the tyrosine residues in the armadillo repeat regions are not phosphorylated. Six of these phosphorylated sites cluster in a short-region upstream of the first arm repeat and fourth ATG start site. The significance of Src phosphorylation at these sites remains to be determined. Nonetheless, post-translational modification of p120ctn may be involved in regulating cell-type specific expression patterns, cellular distribution, and/or downstream signaling.

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