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Inositide ISP

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 Len Stephens
 Peter Evans
 Phillip Hawkins
 Nicholas Ktistakis
 Sonja Vermeren
 Michael Wakelam
 Heidi Welch


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Epigenetics


Inositide


Lymphocyte Signalling
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Nuclear Dynamics


Signalling & Cell Fate


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Sonja Vermeren

Sonja Vermeren

Tel. (01223) 496665
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Research Summary

Neutrophils that did or did not contain ARAP3 were seeded onto glass and allowed to chemotax to a point source of chemoattractant. Cells were time-lapse imaged to visualize cell movement. In the stills shown, the movement of the individual cells was tracked. Control cells moved readily to the micropipette, whilst ARAP3-deficient did not. Stars show the original positions of the micropipette in the control field; this had to be moved to avoid the cells from crawling into the micropipette.

Small GTPases of the Ras superfamily regulate a host of cellular functions including cell motility, adhesion, vesicular transport, cell division and survival. Small GTPases act as molecular switches, cycling between an active, GTP-bound form and an inactive, GDP-bound form. Intrinsic hydrolysis of GTP to GDP is often slow and is catalysed by GTPase activating proteins (GAPs) whilst guanine nucleotide exchange factors (GEFs) catalyse exchange of GDP for GTP.

We recently identified ARAP3 in a screen for novel phosphoinositide 3-OH kinase (PI3K) effectors. ARAP3 is a dual Arf and Rho GAP; it is part of the ARAP family of dual GAPs. ARAP proteins are likely regulator of cross-talk between different families of small G proteins and their regulators such as PI3K. They are likely to have a regulatory role in important cellular functions such as cell motility. Using a mixture of biochemistry and cell biology we characterise the catalytic activities and mode of regulation of ARAP3.

Current projects are also underway to elucidate its physiological function in cells. (More...)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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