MIM-B, a putative metastasis suppressor protein, binds to actin and to protein tyrosine phosphatase delta

Biochem J. 2003 Apr 15;371(Pt 2):463-71. doi: 10.1042/BJ20021962.

Abstract

We have found that MIM-B, a putative metastasis suppressor protein, is implicated in actin cytoskeletal control and interaction with a protein tyrosine phosphatase (PTP). MIM was originally described as a protein whose mRNA was Missing in Metastasis, as it was found not to be present in metastatic bladder carcinoma cell lines [Lee, Y. G., Macoska, J. A., Korenchuk, S. and Pienta, K. J. (2002) Neoplasia 4, 291-294]. We further characterized a variant of MIM, which we call MIM-B, and which we believe may be a link between tyrosine kinase signalling and the actin cytoskeleton. We have shown, using purified proteins and cell extracts, that MIM-B is an actin-binding protein, probably via a WASP (Wiskott-Aldrich syndrome protein)-homology 2 domain at its C-terminus. We have also found that MIM-B binds to the cytoplasmic domain of receptor PTPdelta. Expression of full-length MIM-B induces actin-rich protrusions resembling microspikes and lamellipodia at the plasma membrane and promotes disassembly of actin stress fibres. The C-terminal portion of MIM-B is localized in the cytoplasm and does not affect the actin cytoskeleton when expressed, while the N-terminal portion localizes to internal vesicles and probably targets the protein to membranes. We postulate that MIM-B may be a regulator of actin assembly downstream of tyrosine kinase signalling and that this activity may explain the involvement of MIM in the metastasis of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Genes, Tumor Suppressor
  • Glutathione Transferase / metabolism
  • Kinetics
  • Mice
  • Microfilament Proteins / genetics*
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Protein Binding
  • Protein Tyrosine Phosphatases / metabolism*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Actins
  • MTSS1 protein, human
  • Microfilament Proteins
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • Glutathione Transferase
  • Protein Tyrosine Phosphatases
  • Ptprd protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2