scholarly journals The Carboxyl-terminal Domain of Atypical Protein Kinase Cζ Binds to Ceramide and Regulates Junction Formation in Epithelial Cells

2009 ◽  
Vol 284 (21) ◽  
pp. 14469-14475 ◽  
Author(s):  
Guanghu Wang ◽  
Kannan Krishnamurthy ◽  
Nagavedi S. Umapathy ◽  
Alexander D. Verin ◽  
Erhard Bieberich
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Atypical Protein Kinase ◽  
Terminal Domain ◽  
Carboxyl Terminal Domain ◽  
Junction Formation ◽  
Carboxyl Terminal

scholarly journals The Carboxyl-Terminal Domain of RNA Polymerase II Is Phosphorylated by a Complex Containing cdk9 and Infected-Cell Protein 22 of Herpes Simplex Virus 1

2005 ◽  
Vol 79 (11) ◽  
pp. 6757-6762 ◽  
Author(s):  
Lizette O. Durand ◽  
Sunil J. Advani ◽  
Alice P. W. Poon ◽  
Bernard Roizman
Keyword(s):  
Protein Kinase ◽  
Rna Polymerase Ii ◽  
Cell Protein ◽  
Herpes Simplex Virus 1 ◽  
Rna Pol Ii ◽  
Pol Ii ◽  
Terminal Domain ◽  
Carboxyl Terminal Domain ◽  
Carboxyl Terminal ◽  
Simplex Virus

ABSTRACT The infected-cell protein 22 (ICP22), a regulatory protein encoded by the α22 gene of herpes simplex virus 1, is required for the optimal expression of a set of late viral proteins that includes the products of the US11, UL38, and UL41 genes. ICP22 has two activities. Thus, ICP22 and the UL13 protein kinase mediate the activation of cdc2 and degradation of its partners, cyclins A and B. cdc2 and its new partner, the DNA polymerase accessory factor (UL42), bind topoisomerase IIα in an ICP22-dependent manner. In addition, ICP22 and UL13 mediate an intermediate phosphorylation of the carboxyl terminus of RNA polymerase II (RNA POL II). Here we report another function of ICP22. Thus, ICP22 physically interacts with cdk9, a constitutively active cyclin-dependent kinase involved in transcriptional regulation. A protein complex containing ICP22 and cdk9 phosphorylates in vitro the carboxyl-terminal domain of RNA POL II in a viral US3 protein kinase-dependent fashion. Finally, the carboxyl-terminal domain of RNA POL II fused to glutathione S-transferase is phosphorylated in reaction mixtures containing complexes pulled down with ICP22 or cdk9 immune precipitated from lysates of wild-type parent virus or ΔUL13 but not ΔUS3 mutant-infected cells. The experiments described here place ICP22 and cdk9 in a complex with the carboxyl-terminal domain of RNA POL II. At the same time we confirm the requirement of ICP22 and the UL13 protein kinase in the posttranslational modification of RNA POL II that alters its electrophoretic mobility, although US3 kinase appears to play a role in a cell-type-dependent fashion.

scholarly journals The Carboxyl-Terminal Domain of the Protein Kinase Fused Can Function as a Dominant Inhibitor of Hedgehog Signaling

2002 ◽  
Vol 22 (5) ◽  
pp. 1555-1566 ◽  
Author(s):  
Manuel Ascano ◽  
Kent E. Nybakken ◽  
Janek Sosinski ◽  
Melanie A. Stegman ◽  
David J. Robbins
Keyword(s):  
Protein Kinase ◽  
Critical Role ◽  
Dominant Negative ◽  
Loss Of Function ◽  
Signaling Complex ◽  
Terminal Domain ◽  
Cell Extracts ◽  
Carboxyl Terminal Domain ◽  
Hh Signaling ◽  
Carboxyl Terminal

ABSTRACT The secreted protein hedgehog (Hh) plays a critical role in the developmental patterning of multiple tissues. In Drosophila melanogaster, a cytosolic multiprotein signaling complex appears necessary for Hh signaling. Genes that encode components of this Hh signaling complex (HSC) were originally identified and characterized based on their genetic interactions with hh, as well as with each other. It is only in recent years that the mechanistic functions of these components have begun to be unraveled. Here, we have investigated the relationship between two components of the HSC, the serine/threonine protein kinase Fused (Fu) and the kinesin-related protein Costal2 (Cos2). We have reconstituted a Fu/Cos2 complex in vitro and shown that Fu is able to directly associate with Cos2, forming a complex whose molecular size is similar to a previously described complex found in Drosophila cell extracts. We have also determined that the carboxyl-terminal domain of Fu is necessary and sufficient for the direct binding of Fu to Cos2. To validate the physiological relevance of this interaction, we overexpressed the carboxyl-terminal domain of Fu in wild-type flies. These flies exhibit a phenotype similar to that seen in fu mutants and consistent with an hh loss-of-function phenotype. We conclude that the carboxyl-terminal domain of Fu can function in a dominant negative manner, by preventing endogenous Fu from binding to Cos2. Thus, we provide the first evidence that Hh signaling can be compromised by targeting the HSC for disruption.

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