Association of Lbc Rho guanine nucleotide exchange factor with alpha-catenin-related protein, alpha-catulin/CTNNAL1, supports serum response factor activation
| Autor: | Paola Sterpetti, Keith D. Merdek, Nhan T. Nguyen, Alessandra Tosolini, Brian Park, Deniz Toksoz, Mariam P. Bashar, Parmesh Dutt, Joseph R. Testa |
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| Rok vydání: | 2002 |
| Předmět: |
Serum Response Factor
Recombinant Fusion Proteins Molecular Sequence Data A Kinase Anchor Proteins GTPase Biology Cell Fractionation Biochemistry Cell Line Minor Histocompatibility Antigens Genes Reporter Proto-Oncogene Proteins Two-Hybrid System Techniques Serum response factor Guanine Nucleotide Exchange Factors Humans Amino Acid Sequence Cell adhesion Molecular Biology Gene Actin In Situ Hybridization Fluorescence Adaptor Proteins Signal Transducing Reporter gene Binding Sites Cell Biology Molecular biology Cytoskeletal Proteins Serum Response Element Guanine nucleotide exchange factor Signal transduction Sequence Alignment alpha Catenin Protein Binding |
| Zdroj: | The Journal of biological chemistry. 277(47) |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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