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.
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
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
J. Biol. Chem.
Date: Nov. 22, 2002
PubMed ID: 12270917
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