Insight into the therapeutic aspects of ‘Zeta-Chain Associated Protein Kinase 70kDa’ inhibitors: A review

2014 ◽  
Vol 26 (11) ◽  
pp. 2481-2492 ◽  
Author(s):  
Maninder Kaur ◽  
Manjinder Singh ◽  
Om Silakari
Keyword(s):  
Protein Kinase ◽  
Zeta Chain ◽  
Insight Into

scholarly journals CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1

2018 ◽  
Vol 46 (3) ◽  
pp. 1042-1054 ◽  
Author(s):  
Shu Li ◽  
Jingyi Xue ◽  
Zhipeng Sun ◽  
Tiantian Liu ◽  
Lane Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Confocal Microscopy ◽  
Specific Inhibitor ◽  
Potential Mechanism ◽  
Additional Insight ◽  
Dependent Protein Kinase ◽  
Store Depletion ◽  
Selective Channel ◽  
Dependent Protein ◽  
Insight Into

Background/Aims: Upon Ca2+ store depletion, stromal interaction molecule 1 (STIM1) oligomerizes, redistributes near plasmalemma to interact with Ca2+ selective channel-forming subunit (Orai1) and initiates store-operated Ca2+ entry (SOCE). Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a regulator of SOCE, but how CaMKII regulates SOCE remains obscure. Methods: Using Fura2, confocal microscopy, co-immunoprecipitation, specific blocker and overexpression/knockdown approaches, we evaluated STIM1 aggregation and its interaction with Orai1, and SOCE upon Ca2+ store depletion in thapsigargin (TG) treated HEK293 and HeLa cells. Results: Overexpression of CaMKIIδ enhanced TG-induced STIM1 co-localization and interaction with Orai1 as well as SOCE. In contrast, CaMKIIδ knockdown and a specific inhibitor of CaMKII suppressed them. In addition, overexpression or knockdown of CaMKIIδ in TG treated cells exhibited increased or reduced STIM1 clustering and plasmalemma redistribution, respectively. Conclusion: CaMKII up-regulates SOCE by increasing STIM1 aggregation and interaction with Orai1. This study provides an additional insight into SOCE regulation and a potential mechanism for CaMKII involvement in some pathological situations through crosstalk with SOCE.

scholarly journals Synthetic Lethal Analysis Implicates Ste20p, a p21-activated Protein Kinase, in Polarisome Activation

2003 ◽  
Vol 14 (4) ◽  
pp. 1501-1516 ◽  
Author(s):  
April S. Goehring ◽  
David A. Mitchell ◽  
Amy Hin Yan Tong ◽  
Megan E. Keniry ◽  
Charles Boone ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protein Kinase ◽  
Cell Polarity ◽  
Interacting Proteins ◽  
Substantial Portion ◽  
Lethal Mutant ◽  
Synthetic Lethal ◽  
Mutant Screen ◽  
Insight Into

The p21-activated kinases Ste20p and Cla4p carry out undefined functions that are essential for viability during budding inSaccharomyces cerevisiae. To gain insight into the roles of Ste20p, we have used a synthetic lethal mutant screen to identify additional genes that are required in the absence of Cla4p. Altogether, we identified 65 genes, including genes with roles in cell polarity, mitosis, and cell wall maintenance. Herein, we focus on a set that defines a function carried out by Bni1p and several of its interacting proteins. We found that Bni1p and a group of proteins that complex with Bni1p (Bud6p, Spa2p, and Pea2p) are essential in acla4Δ mutant background. Bni1p, Bud6p, Spa2, and Pea2p are members of a group of polarity determining proteins referred to as the polarisome. Loss of polarisome proteins from acla4Δ strain causes cells to form elongated buds that have mislocalized septin rings. In contrast, other proteins that interact with or functionally associate with Bni1p and have roles in nuclear migration and cytokinesis, including Num1p and Hof1p, are not essential in the absence of Cla4p. Finally, we have found that Bni1p is phosphorylated in vivo, and a substantial portion of this phosphorylation is dependent on STE20. Together, these results suggest that one function of Ste20p may be to activate the polarisome complex by phosphorylation of Bni1p.

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