FIGURE 5.

Cell-penetrating peptide containing the Sdc1-specific β4-binding motif disrupts HER2-dependent haptotaxis and cell survival. TAT peptide is constructed containing the Sdc1-specific binding motif in which Phe-308 necessary for PDZ binding but not for β4 binding is mutated (KQEEAYA) (active peptide) or Phe-308 is mutated along with Tyr-309 necessary for β4 binding (KQEEAAA) (inactive control peptide). A, active or control TAT peptides are tested as competitors of His₆-β4(1677–1752) capture by GST-S1CD or GST-S4CD. B, HaCat keratinocytes are stimulated with LPA and α6β4 integrin clustering antibodies to mimic HER2-dependent matrix chemokinesis or stimulated with EGF to undergo EGFR-dependent chemokinesis in the presence of 0–10 μm TAT peptides. C, MCF10A human breast epithelial cells are stimulated to undergo matrix chemokinesis in the presence of TAT peptides ranging from 0 to 10 μm. D, HaCat keratinocytes, MCF10A mammary epithelium, A431 cervical carcinoma, or HER2-positive SKBr3 breast carcinoma cells were grown for 1 week in the presence of TAT peptide ranging from 0 to 30 μm. Cell death was quantified by trypan blue exclusion. Data represent the mean of six wells ± S.D. (* indicates difference between control and active peptide >0.05.)