Cypher, a striated muscle-restricted PDZ and LIM domain-containing protein, binds to alpha-actinin-2 and protein kinase C

We have cloned and characterized a novel striated muscle-restricted protein (Cypher) that has two mRNA splice variants, designated Cypher1 and Cypher2. Both proteins contain an amino-terminal PDZ domain. Cypher1, but not Cypher2, contains three carboxyl-terminal LIM domains and an amino acid repeat...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-07, Vol.274 (28), p.19807-19813
Main Authors: Zhou, Q, Ruiz-Lozano, P, Martone, M E, Chen, J
Format: Article
Language:English
Subjects:
Actinin - metabolism
Adaptor Proteins, Signal Transducing
Alternative Splicing
Amino Acid Sequence
Animals
Carrier Proteins
Cloning, Molecular
Gene Expression Regulation, Developmental
Homeodomain Proteins
Humans
LIM Domain Proteins
Mice
Molecular Sequence Data
Muscle Proteins - chemistry
Muscle Proteins - genetics
Muscle, Skeletal - metabolism
Myocardium - metabolism
Phosphorylation
Protein Binding
Protein Kinase C - metabolism
RNA, Messenger - genetics
Sequence Alignment
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Summary:We have cloned and characterized a novel striated muscle-restricted protein (Cypher) that has two mRNA splice variants, designated Cypher1 and Cypher2. Both proteins contain an amino-terminal PDZ domain. Cypher1, but not Cypher2, contains three carboxyl-terminal LIM domains and an amino acid repeat sequence that exhibits homology to a repeat sequence found in the largest subunit of RNA polymerase II. cypher1 and cypher2 mRNAs exhibited identical expression patterns. Both are exclusively expressed in cardiac and striated muscle in embryonic and adult stages. By biochemical assays, we have demonstrated that Cypher1 and Cypher2 bind to alpha-actinin-2 via their PDZ domains. This interaction has been further confirmed by immunohistochemical studies that demonstrated co-localization of Cypher and alpha-actinin at the Z-lines of cardiac muscle. We have also found that Cypher1 binds to protein kinase C through its LIM domains. Phosphorylation of Cypher by protein kinase C has demonstrated the functional significance of this interaction. Together, our data suggest that Cypher1 may function as an adaptor in striated muscle to couple protein kinase C-mediated signaling, via its LIM domains, to the cytoskeleton (alpha-actinin-2) through its PDZ domain.
ISSN:0021-9258
DOI:10.1074/jbc.274.28.19807