IP3 y Calcium: FosfatidilInositol como segundos mensajeros intracelulares. - Prof. Llorens, Apuntes de Biotecnología

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IP

Fosfatidil-

Inositol 1,4,5,

trifosfat

(PIP2)

Some Cellular Responses Mediated by G-Protein-linked Receptors Coupled to the Inositol-Phospholipid Signaling Pathway.

Several

second

messengers

are derived

from

phosphatidyli

nositol (PI).

(a) Pathway

for synthesis

of DAG and

IP3, two

important

second

messengers.

Each

membrane-

bound PI

kinase places

a phosphate

The hydrolysis of PI(4,5)P2 by phospholipase C-β. Two intracellular mediators are produced when PI(4,5)P2 is hydrolyzed: inositol 1,4,5-trisphosphate (IP3), which diffuses through the cytosol and releases Ca2+ from the ER, and diacylglycerol, which remains in the membrane and helps to activate the enzyme protein kinase C (see Figure 15-36). There are at least three classes of phospholipase C—β, γ, and σ—and it is the β class that is activated by G- protein-linked receptors. We shall see later that the γ class is activated by a second class of receptors, called receptor tyrosine kinases, that activate the inositol phospholipid signaling pathway without an intermediary G protein.

ATP

PLC  PLC 2

The SH2 domain of phospholipase C gamma-1 is bound to a peptide domain from

the platelet-derived growth factor receptor which includes a phosphotyrosine.

Although not evident in this image, the center of the receptor peptide is hydrophobic,

and the ends, hydrophilic. This interaction activates the phospholipase to cleaves

phosphatidyl inositol bisphosphate to yield the second messengers inositol

trisphosphate (IP3) and diacyl glycerol (DAG), not shown.

Activation of phospholipase C by protein-tyrosine kinases. Phospholipase C-γ (PLC-γ) binds to activated receptor protein-tyrosine kinases via its SH2 domains. Tyrosine phosphorylation increases PLC-γ activity, stimulating the hydrolysis

Hydrolysis of

phospholipids by

phospholipases.

Arrows indicate the

sites of attack for

hydrolytic cleavage

of phospholipases

type A1, A2, C, and

D. The main

products generated

by their action are

also shown. R1/R2:

free fatty acids in

sn -1 or sn -

positions; X:

choline,

ethanolamine,

serine, inositol, and

so forth.