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Revised Manuscript Received June 22, 1993® abstract: A-Myristoylation of pS6kk, a member of the Src family of protein-tyrosine kinases, is essential for its proper targeting to the plasma membrane. 2-Hydroxymyristic acid (HMA) is an analog of myristic acid that becomes metabolically activated in cells to form 2-hydroxymyristoyl-CoA, a potent inhibitor of myristoyl-CoA: protein A-myristoyltransferase (NMT), the enzyme that catalyzes protein A-myristoylation [Paige, L. A., Zheng, G.-q., DeFrees, S. A., Cassady, J. M., & Geahlen, R. L.(1990) Biochemistry 29, 10566]. In the presence of HMA, LSTRA cells, which overexpress p56,£*, synthesized nonmyristoylated p56/l*, which displayed a reduced electrophoretic mobility on SDS-polyacrylamide gels identical to that of a nonmyristoylated Gly2-*•

Ala2 mutant of p56kk. Treatment with myristic acid, 2-hydroxypalmitic acid, or 2-fluoromyristic acid did not result in the synthesis …