AN AUTOREGULATORY REGION IN PROTEIN-KINASE-C - THE PSEUDOANCHORING SITE
AN AUTOREGULATORY REGION IN PROTEIN-KINASE-C - THE PSEUDOANCHORING SITE
复制标题
DOI：
10.1073/pnas.92.2.492
复制
发表时间：
1995-01-17
影响因子：
11.1
通讯作者：
MOCHLYROSEN, D
中科院分区：
文献类型：
--
作者：
RON, D;MOCHLYROSEN, D
我们以前已经鉴定了活化C激酶受体（RACKs）作为蛋白激酶C（PKC）信号传导的组成部分，RACK 1是最近克隆的一种36-kDa的RACK，具有与PKC同源的短序列。配体（PKC）与其细胞内受体（RACK 1）之间的同源序列的一种可能的解释可能是，类似于PKC上的假底物自动调节序列，在酶上还有一个假RACK 1结合位点，如果是这种情况，具有这些序列的肽（来源于RACK 1或PKC）预期影响PKC与RACK 1的体外结合和PKC介导的体内功能。（伪RACK 1肽），而不是其RACK 1同源物，在体外和体内均调节PKC功能。我们的数据表明，伪RACK 1肽在不存在PKC激活剂的情况下结合并激活PKC，从而在体内充当PKC功能的激动剂。因此，PKC中的伪RACK 1序列似乎是另一个自身调节位点;当PKC处于非活性构象时，伪RACK 1位点与RACK结合位点相互作用，PKC的活化暴露了RACK结合位点，使酶与其锚定RACK结合，类似的伪锚定位点可以调节其他蛋白激酶的功能。
We have previously identified receptors for activated C kinase (RACKs) as components of protein kinase C (PKC) signaling, RACK1, a recently cloned 36-kDa RACK, has short sequences of homology to PKC, A possible explanation for the homologous sequences between the ligand (PKC) and its intracellular receptor (RACK1) may be that, similar to the pseudosubstrate autoregulatory sequence on PKC, there is also a pseudo RACK1 binding site on the enzyme, If this is the case, peptides with these sequences (derived from either RACK1 or PKC) are expected to affect PKC binding to RACK1 in vitro and PKC-mediated functions in vivo, Here, we show that the PKC-derived peptide (pseudo-RACK1 peptide), but not its RACK1 homologue, modulated PKC function both in vitro and in vivo, Our data suggest that the pseudo-RACK1 peptide binds and activates PKC in the absence of PKC activators and thereby acts as an agonist of PKC function in vivo. Therefore, the pseudo-RACK1 sequence in PKC appears to be another autoregulatory site; when PKC is in an inactive conformation, the pseudo-RACK1 site interacts with the RACK-binding site, Activation of PKC exposes the RACK-binding site, enabling the association of the enzyme with its anchoring RACK, Similar pseudoanchoring sites may regulate the function of other protein kinases.