Khan I U, Wallin R, Gupta R S, Kammer G M
Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, N. C. 27157, Canada.
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10425-30. doi: 10.1073/pnas.95.18.10425.
Accumulating evidence suggests that the mitochondrial molecular chaperone heat shock protein 60 (hsp60) also can localize in extramitochondrial sites. However, direct evidence that hsp60 functions as a chaperone outside of mitochondria is presently lacking. A 60-kDa protein that is present in the plasma membrane of a human leukemic CD4(+) CEM-SS T cell line and is phosphorylated by protein kinase A (PKA) was identified as hsp60. An 18-kDa plasma membrane-associated protein coimmunoprecipitated with hsp60 and was identified as histone 2B (H2B). Hsp60 physically associated with H2B when both molecules were in their dephospho forms. By contrast, PKA-catalyzed phosphorylation of both hsp60 and H2B caused dissociation of H2B from hsp60 and loss of H2B from the plasma membrane of intact T cells. These results suggest that (i) hsp60 and H2B can localize in the T cell plasma membrane; (ii) hsp60 functions as a molecular chaperone for H2B; and (iii) PKA-catalyzed phosphorylation of both hsp60 and H2B appears to regulate the attachment of H2B to hsp60. We propose a model in which phosphorylation/dephosphorylation regulates chaperoning of H2B by hsp60 in the plasma membrane.
越来越多的证据表明，线粒体分子伴侣热休克蛋白60（hsp60）也可定位于线粒体外的部位。然而，目前缺乏hsp60在线粒体外发挥伴侣功能的直接证据。在人白血病CD4(+) CEM-SS T细胞系的质膜中存在一种60 kDa的蛋白，它可被蛋白激酶A（PKA）磷酸化，该蛋白被鉴定为hsp60。一种18 kDa的与质膜相关的蛋白与hsp60共免疫沉淀，被鉴定为组蛋白2B（H2B）。当hsp60和H2B均处于去磷酸化形式时，它们可发生物理性结合。相比之下，PKA催化的hsp60和H2B的磷酸化导致H2B与hsp60解离，并使完整T细胞质膜上的H2B丢失。这些结果表明：（i）hsp60和H2B可定位于T细胞质膜；（ii）hsp60作为H2B的分子伴侣发挥作用；（iii）PKA催化的hsp60和H2B的磷酸化似乎可调节H2B与hsp60的结合。我们提出了一个模型，其中磷酸化/去磷酸化调节质膜中hsp60对H2B的伴侣作用。
