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Association of Lbc Rho guanine nucleotide exchange factor with alpha-catenin-related protein, alpha-catulin/CTNNAL1, supports serum response factor activation.

The Rho GTPase signaling pathway is required for actin cytoskeletal organization and serum response factor-dependent gene transcription. Lbc is a Rho-specific guanine nucleotide exchange factor that contains a modulatory C-terminal region. To elucidate Lbc regulatory mechanism(s), a yeast two-hybrid screen for proteins that interact with the Lbc C-terminal region was carried out, resulting in multiple isolation of cDNAs encoding the same 734-amino acid Lbc interacting protein. The Lbc interacting protein has homology with the alpha-catenin cell adhesion component and is identical to the alpha-catenin-like alpha-catulin protein of unknown function. The human alpha-catulin gene (CTNNAL1) maps to 9q31-32. Here we identify the predicted endogenous alpha-catulin product, document alpha-catulin and Lbc co-expression in multiple human cell lines, and show alpha-catulin and Lbc subcellular co-fractionation and intracellular localization. The required regions for Lbc and alpha-catulin interaction were mapped, and complex formation between Lbc and alpha-catulin in mammalian cells was detected. Functionally, alpha-catulin co-expression leads to increased Lbc-induced serum response factor activation in vivo as measured by a transcriptional reporter assay. Furthermore, alpha-catulin co-expression enhances Lbc-induced GTP-Rho formation in vivo. These results support the concept that the recently identified alpha-catulin protein may modulate Rho pathway signaling in vivo by providing a scaffold for the Lbc Rho guanine nucleotide exchange factor.

Pubmed ID: 12270917

Authors

  • Park B
  • Nguyen NT
  • Dutt P
  • Merdek KD
  • Bashar M
  • Sterpetti P
  • Tosolini A
  • Testa JR
  • Toksoz D

Journal

The Journal of biological chemistry

Publication Data

November 22, 2002

Associated Grants

  • Agency: NIDDK NIH HHS, Id: 1 P30 DK39428
  • Agency: NCI NIH HHS, Id: CA06927
  • Agency: NCI NIH HHS, Id: CA62029

Mesh Terms

  • A Kinase Anchor Proteins
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Binding Sites
  • Cell Fractionation
  • Cell Line
  • Cytoskeletal Proteins
  • Genes, Reporter
  • Guanine Nucleotide Exchange Factors
  • Humans
  • In Situ Hybridization, Fluorescence
  • Molecular Sequence Data
  • Protein Binding
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Sequence Alignment
  • Serum Response Element
  • Serum Response Factor
  • Two-Hybrid System Techniques
  • alpha Catenin