Transmembrane Neuregulins Interact with LIM Kinase 1, a Cytoplasmic Protein Kinase Implicated in Development of Visuospatial Cognition
| Autor: | Jay Y. Wang, Duanzhi Wen, Kristen Frenzel, Douglas L. Falls |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Williams Syndrome
Molecular Sequence Data Neuromuscular Junction Nerve Tissue Proteins Protein Serine-Threonine Kinases Biology LIMK1 Transfection Biochemistry Receptor tyrosine kinase Lim kinase Animals Integrin-linked kinase Protein kinase A Molecular Biology Glycoproteins Neuregulins LIM domain Muscles Lim Kinases Membrane Proteins Receptor Protein-Tyrosine Kinases Cell Biology Transforming Growth Factor alpha Immunohistochemistry Recombinant Proteins Transmembrane protein Rats Cell biology DNA-Binding Proteins COS Cells biology.protein Neuregulin Protein Kinases Plasmids Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 273:20525-20534 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.273.32.20525 |
| Popis: | The neuregulins are receptor tyrosine kinase ligands that play a critical role in the development of the heart, nervous system, and breast. Unlike many extracellular signaling molecules, such as the neurotrophins, most neuregulins are synthesized as transmembrane proteins. To determine the functions of the highly conserved neuregulin cytoplasmic tail, a yeast two-hybrid screen was performed to identify proteins that interact with the 157-amino acid sequence common to the cytoplasmic tails of all transmembrane neuregulin isoforms. This screen revealed that the neuregulin cytoplasmic tail interacts with the LIM domain region of the nonreceptor protein kinase LIM kinase 1 (LIMK1). Interaction between the neuregulin cytoplasmic tail and full-length LIMK1 was demonstrated by in vitro binding and co-immunoprecipitation assays. Transmembrane neuregulins with each of the three known neuregulin cytoplasmic tail isoforms interacted with LIMK1. In contrast, the cytoplasmic tail of TGF-alpha did not interact with LIMK1. In vivo, neuregulin and LIMK1 are co-localized at the neuromuscular synapse, suggesting that LIMK1, like neuregulin, may play a role in synapse formation and maintenance. To our knowledge, LIMK1 is the first identified protein shown to interact with the cytoplasmic tail of a receptor tyrosine kinase ligand. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|