scholarly journals Altered Morphology and Function of the Lacrimal Functional Unit in Protein Kinase Cα Knockout Mice

2010 ◽  
Vol 51 (11) ◽  
pp. 5592 ◽  
Author(s):  
Zhuo Chen ◽  
Zhijie Li ◽  
Surendra Basti ◽  
William J. Farley ◽  
Stephen C. Pflugfelder
Keyword(s):  
Protein Kinase ◽  
Knockout Mice ◽  
Functional Unit ◽  
Protein Kinase Cα ◽  
And Function

Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney

2011 ◽  
Vol 436 (1) ◽  
pp. 169-179 ◽  
Author(s):  
Laura R. Pearce ◽  
Eeva M. Sommer ◽  
Kei Sakamoto ◽  
Stephan Wullschleger ◽  
Dario R. Alessi
Keyword(s):  
Protein Kinase ◽  
Knockout Mice ◽  
Mammalian Target Of Rapamycin ◽  
The Other ◽  
Downregulated Gene ◽  
S6 Kinase ◽  
Interacting Protein ◽  
Active Complex ◽  
Protein Kinase Cα ◽  
Important Regulator

The mTOR (mammalian target of rapamycin) protein kinase is an important regulator of cell growth and is a key target for therapeutic intervention in cancer. Two complexes of mTOR have been identified: complex 1 (mTORC1), consisting of mTOR, Raptor (regulatory associated protein of mTOR) and mLST8 (mammalian lethal with SEC13 protein 8) and complex 2 (mTORC2) consisting of mTOR, Rictor (rapamycin-insensitive companion of mTOR), Sin1 (stress-activated protein kinase-interacting protein 1), mLST8 and Protor-1 or Protor-2. Both complexes phosphorylate the hydrophobic motifs of AGC kinase family members: mTORC1 phosphorylates S6K (S6 kinase), whereas mTORC2 regulates phosphorylation of Akt, PKCα (protein kinase Cα) and SGK1 (serum- and glucocorticoid-induced protein kinase 1). To investigate the roles of the Protor isoforms, we generated single as well as double Protor-1- and Protor-2-knockout mice and studied how activation of known mTORC2 substrates was affected. We observed that loss of Protor-1 and/or Protor-2 did not affect the expression of the other mTORC2 components, nor their ability to assemble into an active complex. Moreover, Protor knockout mice display no defects in the phosphorylation of Akt and PKCα at their hydrophobic or turn motifs. Strikingly, we observed that Protor-1 knockout mice displayed markedly reduced hydrophobic motif phosphorylation of SGK1 and its physiological substrate NDRG1 (N-Myc downregulated gene 1) in the kidney. Taken together, these results suggest that Protor-1 may play a role in enabling mTORC2 to efficiently activate SGK1, at least in the kidney.

scholarly journals The Last 10 Amino Acid Residues beyond the Hydrophobic Motif Are Critical for the Catalytic Competence and Function of Protein Kinase Cα

2006 ◽  
Vol 281 (41) ◽  
pp. 30768-30781 ◽  
Author(s):  
Sui Sum Yeong ◽  
Yimin Zhu ◽  
Derek Smith ◽  
Chandra Verma ◽  
Wee Guan Lim ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Kinase ◽  
Amino Acid Residues ◽  
Protein Kinase Cα ◽  
Hydrophobic Motif ◽  
And Function

scholarly journals Reproductive Function in Protein Kinase Inhibitor-Deficient Mice

2001 ◽  
Vol 21 (12) ◽  
pp. 3959-3963 ◽  
Author(s):  
Mouna Belyamani ◽  
Esha A. Gangolli ◽  
Rejean L. Idzerda
Keyword(s):  
Protein Kinase ◽  
Knockout Mice ◽  
Nuclear Export ◽  
Kinase Inhibitor ◽  
Physiological Role ◽  
Reproductive Function ◽  
Protein Kinase Inhibitor ◽  
Double Knockout ◽  
Genes Encoding ◽  
And Function

ABSTRACT The protein kinase inhibitor (PKI) family includes three genes encoding small, heat-stable inhibitors of the cyclic AMP-dependent kinase PKA. Each PKI isoform contains a PKA inhibitory domain and a nuclear export domain, enabling PKI to both inhibit PKA and remove it from the nucleus. The PKIβ isoform, also known as testis PKI, is highly expressed in germ cells of the testis and is found at more modest levels in other tissues. In order to investigate its physiological role, we have generated PKIβ knockout mice by gene targeting. These mice exhibit a partial loss of PKI activity in testis but remain fertile with normal testis development and function. PKIβ knockout females also reproduce normally. The PKIβ mutants were crossed with our previously derived PKIα mutants to obtain double-knockout mice. Remarkably, these mice are also viable and fertile with no obvious physiological defects in either males or females.

Spatial control of actin-based motility through plasmalemmal PtdIns(4,5)P2-rich raft assemblies.

2005 ◽  
Vol 72 ◽  
pp. 119-127 ◽  
Author(s):  
Tamara Golub ◽  
Caroni Pico
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Actin Cytoskeleton ◽  
Lipid Rafts ◽  
Patch Clustering ◽  
Pkc Protein Kinase C ◽  
Membrane Bound ◽  
And Function ◽  
Cytoskeleton Dynamics ◽  
Syndrome Protein

The interactions of cells with their environment involve regulated actin-based motility at defined positions along the cell surface. Sphingolipid- and cholesterol-dependent microdomains (rafts) order proteins at biological membranes, and have been implicated in most signalling processes at the cell surface. Many membrane-bound components that regulate actin cytoskeleton dynamics and cell-surface motility associate with PtdIns(4,5)P2-rich lipid rafts. Although raft integrity is not required for substrate-directed cell spreading, or to initiate signalling for motility, it is a prerequisite for sustained and organized motility. Plasmalemmal rafts redistribute rapidly in response to signals, triggering motility. This process involves the removal of rafts from sites that are not interacting with the substrate, apparently through endocytosis, and a local accumulation at sites of integrin-mediated substrate interactions. PtdIns(4,5)P2-rich lipid rafts can assemble into patches in a process depending on PtdIns(4,5)P2, Cdc42 (cell-division control 42), N-WASP (neural Wiskott-Aldrich syndrome protein) and actin cytoskeleton dynamics. The raft patches are sites of signal-induced actin assembly, and their accumulation locally promotes sustained motility. The patches capture microtubules, which promote patch clustering through PKA (protein kinase A), to steer motility. Raft accumulation at the cell surface, and its coupling to motility are influenced greatly by the expression of intrinsic raft-associated components that associate with the cytosolic leaflet of lipid rafts. Among them, GAP43 (growth-associated protein 43)-like proteins interact with PtdIns(4,5)P2 in a Ca2+/calmodulin and PKC (protein kinase C)-regulated manner, and function as intrinsic determinants of motility and anatomical plasticity. Plasmalemmal PtdIns(4,5)P2-rich raft assemblies thus provide powerful organizational principles for tight spatial and temporal control of signalling in motility.

Loss of gap junctions in biliary atresia occurs simultaneously with declined expression of Protein kinase Cα

2015 ◽  
Vol 53 (01) ◽  
Author(s):  
JHK Andruszkow ◽  
S Groos ◽  
C Klaus ◽  
U Schneider ◽  
C Petersen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Gap Junctions ◽  
Biliary Atresia ◽  
Protein Kinase Cα

Transfection with Protein Kinase Cα Confers Increased Multidrug Resistance to MCF-7 Cells Expressing P-Glycoprotein

1991 ◽  
Vol 3 (6) ◽  
pp. 181-189 ◽  
Author(s):  
Gang Yu ◽  
Shakeel Ahmad ◽  
Angelo Aquino ◽  
Craig R. Fairchild ◽  
Jane B. Trepel ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Protein Kinase ◽  
P Glycoprotein ◽  
Protein Kinase Cα ◽  
Mcf 7

scholarly journals Novel Therapeutic Targets in Heart Failure: The Phospholipase Cβ1b–Shank3 Interface

2015 ◽  
Vol 7 ◽  
pp. CMT.S18480
Author(s):  
Elizabeth A. Woodcock ◽  
David R. Grubb
Keyword(s):  
Heart Failure ◽  
Protein Kinase ◽  
Inotropic Agents ◽  
Specific Enzyme ◽  
Pump Performance ◽  
New Class ◽  
Promising Target ◽  
Protein Kinase Cα ◽  
Myocyte Contractility ◽  
Contractile Performance

Inotropic agents are often used to improve the contractile performance of the failing myocardium, but this is often at a cost of increased myocardial ischemia and arrhythmia. Myocyte contractility depends on the release of Ca2+ from the sarcoplasmic reticulum, and this Ca2+ is subject to regulation by the phosphorylation status of phospholamban (PLN). Many currently used inotropic agents function by increasing the phosphorylation of PLN, but these also heighten the risk of ischemia. Another approach is to reduce the dephosphorylation of PLN, which can be achieved by inhibiting pathways upstream or downstream of the protein kinase Cα. Phospholipase Cβ1b is responsible for activating protein kinase Cα, and its activity is substantially heightened in failing myocardium. We propose phospholipase Cβ1b, a cardiac-specific enzyme, as a promising target for the development of a new class of inotropic agents. By reversing changes that accompany the transition to heart failure, it may be possible to provide well-tolerated improvement in pump performance.

scholarly journals Alcohol/Cholecystokinin-evoked Pancreatic Acinar Basolateral Exocytosis Is Mediated by Protein Kinase Cα Phosphorylation of Munc18c

2007 ◽  
Vol 282 (17) ◽  
pp. 13047-13058 ◽  
Author(s):  
Laura I. Cosen-Binker ◽  
Patrick P. L. Lam ◽  
Marcelo G. Binker ◽  
Joseph Reeve ◽  
Stephen Pandol ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Cα
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