T. Iiri et al., POTENTIATION OF G(I)-MEDIATED PHOSPHOLIPASE-C ACTIVATION BY RETINOIC ACID IN HL-60 CELLS - POSSIBLE ROLE OF G(GAMMA-2), The Journal of biological chemistry, 270(11), 1995, pp. 5901-5908
Differentiated HL-60 cells acquire responsiveness to fMet-Leu-Phe (fML
P), which activates phospholipase C and O-2(-) generation in a pertuss
is toxin-sensitive manner. Addition of retinoic acid (RA) for the last
24 h during dimethyl sulfoxide (Me(2)SO)-induced differentiation enha
nced fMLP dependent signals and interaction between fMLP receptor and
G(i). RA modifies both the function and subunit composition of G(i2),
the predominant G(i) of HL-60 membranes, as shown by comparing purifie
d G(i2) from membranes of Me(2)SO-treated cells (D-G(i2)) to G(i) from
membranes of cells treated with both Me(2)SO and RA (DR-G(i2)). As co
mpared to D-G(i2), DR-G(i2) induced more fMLP binding when added to me
mbranes of pertussis toxin treated HL-60 cells and, in the presence of
GTP gamma S, stimulated beta gamma-sensitive phospholipase C in extra
cts of HL-60 cells to a much greater extent and at lower concentration
s. Immunoblots revealed that RA induced expression of the gamma(2) sub
unit, which was otherwise undetectable in G(i2) purified from HL-60 ce
lls or in HL-60 membranes. Possibly by inducing expression of gamma(2)
, RA alters two functions of the G(i) beta gamma subunit, modulation o
f fMLP receptor-G(i2) coupling and activation of the effector, phospho
lipase C.