Sunday, July 10, 2016

Integrins again? Is there anything they aren't involved in?

Man, these stupid integrins. It seems like if you dig deep enough they are involved in everything!

More evidence that these ridiculously complex sensor/activator things are something we should be considering? 

This solid paper that indicates how critical integrinB1 is in the aging process in mice. Normal integrin levels? Mouse that dunks like young Doctor J. Knock out the integrinB1? Mouse that dunks like older Doctor J.

Wait. Bad example.You get it, though. They also restore ItgB1 function (not in the good Doctor -- in an old mouse) and the mouse immediately does a keg stand (or something -- weird. no Google Images of a mouse doing a keg stand? Oh well...).

The paper then diverges off into looking at what ItgB1 is typically activated by (fibronectin) and do a bunch of nice western blots to look at 4 or 5 proteins downstream of ItgB1.  Their conclusions are that they should probably think about other integrins. Hmmm...I wonder how they might go about that....?  Wait!  I know how!

In this awesome paper a few years ago, this group developed a complete model system for studying downstream ItgB1 family signaling. They used SILAC and an Orbitrap Velos, and their heat maps are sick (seriously, the group in the paper I mentioned first have pretty western blots. Someone has either done a million blots in their career or they tried 50 times to get that blot right. Then you look at the heat maps in the Max Planck this even science from the same planet...or century...?)

Seriously, we can EASILY identify/quantify virtually every known protein downstream of ItgB1. With the exception of some phosphorylation sites that are embedded in lysine-rich motifs and some kinases that require cytokine pulldowns this is a problem proteomics solved the crap out of 5 years ago when everyone was developing these awesome techniques (and kits) for applying proteomics to these central pathways --mostly for cancer. Got the tools and (hopefully) and easier problem to solve!

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