… as I use this here blog for wholly selfish (but educational!) purposes.

You see, I am someone for whom learning science often amounts to writing out mechanisms/processes over and over and over again. In psychopharmacology two years ago, a friend and I would regularly mark up whole chalkboards as we attempted to remember what this neurotransmitter did as opposed to that neurotransmitter.

So now, in this “post,” I plan to reason out for myself the PIP2-Calcium signaling mechanism, which I’ve been having trouble remembering. Feel free to zone out/not read any further because, quite frankly, I’m writing now for my own understanding, not others’ entertainment.

Why put it in Grub First, then? Because it’s my blog, dammit! No, really– publishing something necessitates I read it over several times and understand it myself. Really put in the effort, if you will.

If for some odd reason you feel like learning about how this particular hormone signaling process works, then by all means, read on!

PIP2-Calcium signaling

PIP2-Calcium, or PIP2-C, is a second messenger system not unlike that of cyclic adenosine monophosphate (cAMP). Because the hormones that make use of this activation mechanism (which are all amino acid-based, notably oxytocin, epinephrine, anti-diuretic hormone and gonadotropin-releasing hormone) are water-soluble and thus unable to diffuse across the lipid bilayer of a cell membrane, their target receptors exist on the surface of cell membranes. This is in contrast to the class of steroid hormones, which are lipid-soluble and can thus easily diffuse across the lipid bilayer.

In the cAMP second messenger system, the hormone (the “first messenger”) binds to its extracellular receptor, changing the shape of the receptor and thereby exposing a binding site for a G protein, which I like to refer as a “Guide” protein. As the G protein binds to the receptor in question, it exchanges a guanosine diphosphate (GDP) for a guanosine triphosphate (GTP) molecule, thereby allowing the G protein to move along the inner membrane and activating an enzyme known as adenylate cyclase. Adenylate cyclase will further generate cyclic adenosine monophosphate (again, cAMP), which will in turn activate enyzmes known as protein kinases to add phosphate groups to proteins at will, causing cellular changes.

The PIP2-C system is more confusing to me. In PIP2-C signaling, the hormone (oxytocin, let’s say) binds to a extracellular target receptor, activating a G protein via the same GDP/GTP swap as discussed above. The G protein in this case activates an enzyme known as phospholipase C, which might best be thought of as the equivalent of the adenylate cyclase of the cAMP system. Phospholipase C breaks down the membrane phospholipid PIP2 to yield inositol triphosphate (IP3) and diaglycerol (DAG), both of which are considered to be 2nd messengers much like cAMP. DAG in this case will activate protein kinase enzymes, while IP3 will head over to the endoplasmic reticulum, where it will bind to an IP3-specific receptor, which also happens to be a calcium ion channel. Once bound to its receptor, IP3 causes the channel to release calcium from the endoplasmic reticulum.

So there it is. It makes more sense to me, now that I’ve written it out. Yay for catering to your own learning style!

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