Increased phosphatidylinositol kinase activity in psoriatic epidermis.
Phosphatidylinositol (PI) kinase is activated by growth factors, such as epidermal growth factor (EGF), and is thought to be involved in cellular proliferation. Psoriasis is a hyperproliferative epidermal disease in which EGF receptor expression is altered and phospholipase C activity is increased. Considering the potential importance of growth factor stimulated phosphoinositide metabolism in the genesis of abnormal growth, we measured PI kinase activity in epidermal keratome biopsies from normal skin and the lesional and nonlesional skin of psoriatic patients. The PI kinase activity in 10 psoriatic involved plaques was increased 6.7-fold (Vmax = 67.1 +/- 23.9 pmol formed/min/mg protein +/- SE) when compared with 11 normal epidermal biopsies (Vmax = 10.0 +/- 1.3 pmol/min/mg protein, p less than 0.025). Similar results were noted when enzyme activity was standardized using DNA content. The apparent Km of PI kinase for ATP in involved psoriatic biopsies (0.45 +/- 0.14 mM) was also significantly (p less than 0.025) increased compared with normals (0.11 +/- 0.02 mM). The PI kinase activity in 11 biopsies of nonlesional psoriatic epidermis was not statistically different from normal epidermis. Both psoriatic and normal PI kinases required Mg++ and were inhibited by Ca++. The polyamine, spermine, a known activator of PI kinase in other tissues, stimulated normal but not psoriatic epidermal PI kinase. Both normal and psoriatic PI kinase activities had an apparent mol wt of 85,000. Increased synthesis of phosphoinositides by PI kinase in psoriatic tissue may provide more substrate for phospholipase C; a key enzyme in growth factor-mediated signal transduction.
Pike
M C
MC
Arthritis Unit, Massachusetts General Hospital, Boston 02114.
Lee
C S
CS
Elder
J T
JT
Voorhees
J J
JJ
Fisher
G J
GJ
D019870:1-Phosphatidylinositol 4-Kinase; D000241:Adenosine / Q000494:pharmacology; D002413:Cations, Divalent / Q000032:analysis; D002846:Chromatography, Affinity; D003524:Cyclosporins / Q000494:pharmacology; D003902:Detergents; D004817:Epidermis / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010770:Phosphotransferases / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology; D011565:Psoriasis / Q000201:enzymology*; D012016:Reference Values; D012995:Solubility
D002413:Cations, Divalent; D003524:Cyclosporins; D003902:Detergents; D011073:Polyamines; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D000241:Adenosine