scholarly journals Tension on JAM-A activates RhoA via GEF-H1 and p115 RhoGEF

2016 ◽  
Vol 27 (9) ◽  
pp. 1420-1430 ◽  
Author(s):  
David W. Scott ◽  
Caitlin E. Tolbert ◽  
Keith Burridge

Junctional adhesion molecule A (JAM-A) is a broadly expressed adhesion molecule that regulates cell–cell contacts and facilitates leukocyte transendothelial migration. The latter occurs through interactions with the integrin LFA-1. Although we understand much about JAM-A, little is known regarding the protein’s role in mechanotransduction or as a modulator of RhoA signaling. We found that tension imposed on JAM-A activates RhoA, which leads to increased cell stiffness. Activation of RhoA in this system depends on PI3K-mediated activation of GEF-H1 and p115 RhoGEF. These two GEFs are further regulated by FAK/ERK and Src family kinases, respectively. Finally, we show that phosphorylation of JAM-A at Ser-284 is required for RhoA activation in response to tension. These data demonstrate a direct role of JAM-A in mechanosignaling and control of RhoA and implicate Src family kinases in the regulation of p115 RhoGEF.

2010 ◽  
Vol 10 ◽  
pp. 1450-1461 ◽  
Author(s):  
Haya Sarras ◽  
Solmaz Alizadeh Azami ◽  
J. Peter McPherson

BCLAF1 was originally identified as a protein that interacts with antiapoptotic members of the Bcl2 family. Initial studies indicated a role for this protein as an inducer of apoptosis and repressor of transcription. Subsequent studies have shown that BCLAF1 plays criticals roles in a wide range of processes that are not normally associated with actions of Bcl2 family members, including lung development, T-cell activation, and control of the lytic infection program of Kaposi's sarcoma–associated herpesvirus. Here, we provide an overview of findings from past studies that both support and challenge the role of BCLAF1 in cell death and transcriptional control. We also present recent findings from our laboratory and others indicating a role for BCLAF1 in post-transcriptional processes that impact mRNA metabolism, instead of a direct role for this protein in apoptosis or transcription.


2014 ◽  
Vol 48 (6) ◽  
pp. 1137-1144 ◽  
Author(s):  
Maria Clara Padoveze ◽  
Rosely Moralez de Figueiredo

Little research has been conducted to date on the role of primary health care (PHC) in the prevention of healthcare associated infections (HCAIs). The present article is a theoretical study of the principle of primum non nocere and aims to promote reflection on the role of PHC in HCAI prevention with emphasis on practical recommendations. The indirect and direct roles of PHC in HCAI prevention are debated in light of this guiding principle. With respect to the indirect role of PHC, we discuss the issues of hospital-centrism and ambulatory care-sensitive conditions. The article outlines a number of challenges faced by health services related to PHC’s direct role in HCAI prevention, highlights seven key components of HCAI prevention programmes within the PHC sphere and provides practical recommendations for HCAI control and prevention.



1982 ◽  
Vol 208 (1) ◽  
pp. 205-210 ◽  
Author(s):  
U Padel ◽  
C Unger ◽  
H D Söling

The present study was undertaken to investigate a possible involvement of phospholipid methyltransferases in the coupling of receptor-mediated stimulation to secretion. Phospholipid methyltransferases were assayed in isolated parotid acini in the presence of carbamoylcholine or isoprenaline. Carbamoylcholine reduced the incorporation of methyl groups into phospholipids, whereas isoprenaline showed no effect. Amylase secretion stimulated either by carbamoylcholine or by isoprenaline could not be affected by inhibitors of methyltransferases (3-deaza-adenosine alone or plus homocysteine thiolactone) under conditions where phospholipid methylation was strongly inhibited. The activity of adenylate cyclase in isolated parotid microsomal membranes was not inhibited or stimulated by S-adenosyl-homocysteine or -methionine respectively. These results indicate that phospholipid methylation does not play an essential role in stimulus-secretion coupling in the parotid gland.


2014 ◽  
Vol 6 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Shivani Sharma ◽  
Chintda Santiskulvong ◽  
Jianyu Rao ◽  
James K. Gimzewski ◽  
Oliver Dorigo

Measurements of cell stiffness, IC50 and cellular actin stress fiber organization reveal a direct role of Rho mediated actin remodeling mechanism in cisplatin resistance of ovarian cancer cells.


1983 ◽  
Vol 98 (1) ◽  
pp. 71-77 ◽  
Author(s):  
J. K. Olynyk ◽  
N. W. Bruce ◽  
B. J. Waddell

The role of placental luteotrophins in modulating plasma progesterone concentrations and ovarian progesterone secretion was examined in 16-day pregnant rats. In an initial experiment rats were placentectomized and their plasma progesterone concentrations monitored for 24 h; the rats were conscious within 30 min of placentectomy. Relative to control values, progesterone concentrations fell significantly within 0·5 h. A venous outflow technique was then used to monitor rates of progesterone secretion from ovaries of hysterectomized and control rats maintained under anaesthesia. Hysterectomy had no apparent effect on either progesterone secretion or plasma progesterone concentrations for at least 2 h. A final experiment was carried out to compare the effects of hysterectomy on plasma progesterone concentrations in conscious rats with those of placentectomized rats of the first experiment. Progesterone concentrations did not change significantly in hysterectomized rats for 4 h but fell to very low values by 24 h. These results suggest that placental luteotrophins do not have an acute, direct role in the control of plasma progesterone levels but are needed to maintain progesterone secretion in the longer term and possibly inhibit uterine luteolysin release.


Author(s):  
R. F. Zeigel ◽  
W. Munyon

In continuing studies on the role of viruses in biochemical transformation, Dr. Munyon has succeeded in isolating a highly infectious human herpes virus. Fluids of buccal pustular lesions from Sasha Munyon (10 mo. old) uiere introduced into monolayer sheets of human embryonic lung (HEL) cell cultures propagated in Eagles’ medium containing 5% calf serum. After 18 hours the cells exhibited a dramatic C.P.E. (intranuclear vacuoles, peripheral patching of chromatin, intracytoplasmic inclusions). Control HEL cells failed to reflect similar changes. Infected and control HEL cells were scraped from plastic flasks at 18 hrs. of incubation and centrifuged at 1200 × g for 15 min. Resultant cell packs uiere fixed in Dalton's chrome osmium, and post-fixed in aqueous uranyl acetate. Figure 1 illustrates typical hexagonal herpes-type nucleocapsids within the intranuclear virogenic regions. The nucleocapsids are approximately 100 nm in diameter. Nuclear membrane “translocation” (budding) uias observed.


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