Pericentrin anchors protein kinase A at the centrosome through a newly identified RII-binding domain

被引:109
作者
Diviani, D
Langeberg, LK
Doxsey, SJ
Scott, JD
机构
[1] Oregon Hlth Sci Univ, Howard Hughes Med Inst, Portland, OR 97201 USA
[2] Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA
[3] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA USA
关键词
D O I
10.1016/S0960-9822(00)00422-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Centrosomes orchestrate microtubule nucleation and spindle assembly during cell division [1,2] and have long been recognized as major anchoring sites for cAMP-dependent protein kinase (PKA) [3,4]. Subcellular compartmentalization of PKA is achieved through the association of the PKA holoenzyme with A-kinase anchoring proteins (AKAPs) [5,6]. AKAPs have been shown to contain a conserved helical motif, responsible for binding to the type II regulatory subunit (RII) of PKA, and a specific targeting motif unique to each anchoring protein that directs the kinase to specific intracellular locations. Here, we show that pericentrin, an integral component of the pericentriolar matrix of the centrosome that has been shown to regulate centrosome assembly and organization, directly interacts with PKA through a newly identified binding domain. We demonstrate that both RII and the catalytic subunit of PKA coimmunoprecipitate with pericentrin isolated from HEK-293 cell extracts and that PKA catalytic activity is enriched in pericentrin immunoprecipitates. The interaction of pericentrin with RII is mediated through a binding domain of 100 amino acids which does not exhibit the structural characteristics of similar regions on conventional AKAPs. Collectively, these results provide strong evidence that pericentrin is an AKAP in vivo. (C) 2000 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:417 / 420
页数:4
相关论文
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