Hormones ganglioside effect

We have shown that the inhibitory effect of GM3 on EGF receptor Tyr kinase of A431 cells is greatly enhanced in the presence of lyso-phosphatidylcho-line (lyso-PC), but not lyso-phosphatidylethanolamine, lyso-phosphatidylserine, or lyso-phosphatidylinositol (Igarashi et ai, 1990). In an in vitro assay system, lyso-PC (but not the other compounds listed above) greatly stimulated EGF-dependent Tyr phosphorylation of EGF receptor. It is therefore assumed that lyso-PC promotes the inhibitory effect of GM3 in modulation of EGF receptor kinase (RK). Figure 1 illustrates the possible cooperative effect between lyso-PC and GM3, and specificities of ganglioside effects on various growth factor and hormone receptors. 

Since the effect of TSH on TPMP+ uptake precedes the effect of the hormone on adenylate cyclase activity,1 7 the possibility exists that a primary mode of action of each of these effectors is to alter electrochemical ion gradients across the cell membrane. This concept is attractive in that it would serve to explain certain other findings. Thus, hCG causes changes in adrenal cell ion transport which not only precede adenylate cyclase stimulation, but occur at concentrations of the effector which have minimal effects on cyclase activity 1 9 cholera toxin and its B protein induce alterations in the permeability of liposomes reconstituted with "receptor" ganglioside in the absence of adenylate cyclase.50 51... 

Addition of mixed gangliosides abolished the stimulatory effect of cholera toxin on progesterone production in isolated rat ovarian cells, but had no influence on the effect of gonadotropin. It was concluded that gangliosides were not involved in hormone-receptor interactions. 

FIGURE 1. Cooperative effect of lyso-PC and GM3 on EGF RK activity. (Upper panel) Specificity of effect of gangliosides (shown on left) on various receptors for growth factors and hormones (shown on right). , inhibitory effect 0, enhancing effect. Some of these effects occur via inhibition or promotion of receptor-associated tyrosine kinases (Lower panel). Cooperative effect of lyso-PC and GM3 in suppression of EGF RK activity. EGF (E), when bound to its receptor (ER), activates receptor-associated protein kinase (PK) (this mechanism is further illustrated in Figure 2). EGF-dependent activation of PK is promoted by lyso-PC (derived from PC) (route 1). GM3 inhibits PK, particularly in cooperation with lyso-PC (route 3). Lyso-GM3 (derived from GM3 by removal of fatty acyl group) also inhibits PK (route 2). 

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