The ankyrin-binding domain of CD44s is involved in regulating hyaluronic acid-mediated functions and prostate tumor cell transformation.

CD44 isoforms, such as CD44s (the standard form), contain at least one ankyrin-binding site within the 70-amino acid (aa) cytoplasmic domain and several hyaluronic acid (HA)-binding sites within the extracellular domain. To study the role of CD44s-ankyrin interaction in regulating human prostate tumor cells, we have constructed several CD44s cytoplasmic ...
deletion mutants that lack the ankyrin-binding site(s). These truncated cDNAs were stably transfected into CD44-negative human prostate tumor cells (LNCaP). Our results indicate that a critical region of 15-amino acids (aa) between aa 304 and aa 318 of CD44s is required for ankyrin binding. Biochemical analyses, using competition binding assays with a synthetic peptide containing the 15 aa between aa 304 and aa 318 (NSGNGAVEDRKPSGL), further support the conclusion that this region contains the ankyrin-binding domain of CD44s. Deletion of this 15-aa ankyrin-binding sequence from CD44s results in a drastic reduction of HA-mediated binding/cell adhesion, Src p60 kinase(s) interaction and anchorage-independent growth in soft agar. These findings suggest that the binding of cytoskeletal proteins, such as ankyrin, to the cytoplasmic domain of CD44s plays a pivotal role in regulating HA-mediated functions as well as Src kinase activity and prostate tumor cell transformation.
Mesh Terms:
Amino Acid Sequence, Ankyrins, Antigens, CD44, Carrier Proteins, Cell Adhesion, Cell Division, Cell Transformation, Neoplastic, DNA, Complementary, Humans, Hyaluronic Acid, Male, Microfilament Proteins, Molecular Sequence Data, Peptides, Prostatic Neoplasms, Protein Binding, Proto-Oncogene Proteins pp60(c-src), Recombinant Fusion Proteins, Sequence Deletion, Spectrin, Tumor Cells, Cultured
Cell Motil. Cytoskeleton
Date: Mar. 31, 1998
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