C-TERMINAL CTII MOTIF OF 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASEUNDERGOES CARBOXYLMETHYLATION

Eukaryotic proteins with a carboxyl-terminal CaaX motif are modified b y isoprenylation and subsequently processed by proteolysis of the thre e terminal amino acids and carboxylmethylation of the exposed cysteine residue, The myelination-associated 2',3'-cyclic nucleotide 3'-phosph odiesterase (CNP) has a C-terminal CTII sequence and is isoprenylated; however, no examples of subsequent processing exist when threonine, a polar residue, is located adjacent to the cysteine, Here we show that CNP is capable of being carboxylmethylated in both insect cells and g lioma cells, This processing is dependent upon isoprenylation of the c ysteine and can be inhibited with the isoprenylated cysteine derivativ e, N-acetyl-S-farnesyl-L-cysteine. Although the role of the methyl gro up at the C-terminus of other isoprenylated proteins is not fully unde rstood, modulation of signal transduction pathways is strongly indicat ed. This modification of CNP may similarly regulate cell biological pr ocesses in myelinogenesis. (C) 1994 Wiley-Liss, Inc.