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Previous Article | Next Article
Volume 16, Number 21, Issue of November 1, 1996 pp. 6784-6794
Copyright ©1996 Society for NeuroscienceRin, a Neuron-Specific and Calmodulin-Binding Small G-Protein, and Rit Define a Novel Subfamily of Ras Proteins
Received May 29, 1996; revised July 29, 1996; accepted Aug. 12, 1996.
Ching-Hsien J. Lee1, 2, Neil G. Della1, Christina E. Chew1, and Donald J. Zack1, 2, 3 1 Wilmer Eye Institute, and Departments of 2 Neuroscience and 3 Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9289
cDNAs encoding two novel 25 kDa Ras-like proteins, Rit and Rin, were isolated from mouse retina using a degenerate PCR-based cloning strategy. Using the expressed sequence tag database, human orthologs were also obtained and sequenced. The protein sequences of Rit and Rin, which are 64% identical, are more similar to each other than to any known Ras protein. Their closest homologs in the databases are Mucor racemosus Ras2 and Ras3, to which they show ~48% identity. Rit and Rin both bind GTP in vitro. An unusual feature of their structure is that they lack a known recognition signal for C-terminal lipidation, a modification that is generally necessary for plasma membrane association among the Ras subfamily of proteins. Nonetheless, transiently expressed Rit and Rin are plasma membrane-localized. Both proteins contain a C-terminal cluster of basic amino acids, which could provide a mechanism for membrane association. Deletion analysis suggested that this region is important for Rit membrane binding but is not necessary for Rin. Rit, like most Ras-related proteins, is ubiquitously expressed. Rin, however, is unusual in that it is expressed only in neurons. In addition, Rin binds calmodulin through a C-terminal binding motif. These results suggest that Rit and Rin define a novel subfamily of Ras-related proteins, perhaps using a new mechanism of membrane association, and that Rin may be involved in calcium-mediated signaling within neurons.
Key words: small G-protein; Ras-like protein; CAAX box; calcium signaling; signal transduction; neuron-specific; calmodulin
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