The perplexing case of the geranylgeranyl transferase-deficient mouse.
Proteins that end with a CAAX sequence are targeted to cellular membranes by a series of posttranslational modifications that include prenylation, proteolysis, and carboxyl methylation. Two prenyltransferases modify CAAX proteins: farnesyltransferase and geranylgeranyltransferase type I (GGTase-I). Rho family GTPases that control the actin cytoskeleton and are therefore critical to inflammatory cell function are substrates for GGTase-I. In this issue of the JCI, Khan et al. examined mice in which GGTase-I was conditionally deleted in macrophages. Rather than obtunded cells, the authors found activated Rho proteins in fully functional macrophages that hypersecreted inflammatory cytokines and induced an erosive, inflammatory arthritis. This surprising result calls into question the role of protein geranylgeranylation in inflammatory cell signaling.
NYU Cancer Institute, Smilow 1207, 522 First Avenue, New York, New York 10016, USA. mark.philips@nyumc.org
Mark R
MR
Philips
D019883:Alkyl and Aryl Transferases / Q000172:deficiency* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D051231:Farnesyltranstransferase / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D054876:Prenylation; D015398:Signal Transduction / Q000276:immunology; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; D020741:rho GTP-Binding Proteins
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