Díaz-Meco M T, Municio M M, Frutos S, Sanchez P, Lozano J, Sanz L, Moscat J
Centro de Biología Molecular Consejo Superior de Investigaciones Cientificas Universidad Autónoma de Madrid.
Cell. 1996 Sep 6;86(5):777-86. doi: 10.1016/s0092-8674(00)80152-x.
The atypical PKCs are involved in a number of important cellular functions, including cell proliferation. We report here that the product of the par-4 gene specifically interacts with the regulatory domains of zeta PKC and lambda/LPKC, which dramatically inhibits their enzymatic activity. This is particularly challenging, because expression of par-4 has been shown to correlate with growth inhibition and apoptosis. Results are shown here demonstrating that the expression of par-4 in NIH-3T3 cells induces morphological changes typical of apoptosis, which are abrogated by cotransfection of either wild-type zeta PKC or lambda/LPKC, but not by their respective kinase-inactive mutants. These findings support a role for the atypical PKC subspecies in the control of cell growth and survival.
非典型蛋白激酶C参与多种重要的细胞功能,包括细胞增殖。我们在此报告,par-4基因的产物特异性地与ζ蛋白激酶C和λ/ι蛋白激酶C的调节结构域相互作用,这显著抑制了它们的酶活性。这尤其具有挑战性,因为已表明par-4的表达与生长抑制和细胞凋亡相关。此处展示的结果表明,par-4在NIH-3T3细胞中的表达诱导了典型的细胞凋亡形态变化,共转染野生型ζ蛋白激酶C或λ/ι蛋白激酶C可消除这些变化,但共转染它们各自的激酶失活突变体则不能。这些发现支持非典型蛋白激酶C亚类在细胞生长和存活控制中的作用。