Human neuroblastoma cell differentiation requires protein kinase C-theta

Neuroblastoma LAN-5 cells exposed to retinoic acid cease to multiply and ex tend neurite outgrowths acquiring a neuronal phenotype. We now report that protein kinase C-theta (PKC-theta) isozyme is involved in this differentiat ion process due to the following findings: (i) PKC-theta is expressed by LA N-5 cells as a nuclear and perinuclear protein; (ii) cell stimulation with retinoic acid promotes in a large increase in the expression level of the k inase and its intracellular redistribution; and (iii) a PKC-theta antisense oligonucleotide reduces at the same time the expression level of the kinas e and the cell response to retinoic acid. Altogether these data are consist ent with a specific role played by PKC-theta in the differentiation program of neuronal cells. (C) 2000 Academic Press.