MUTANT RAT PHOSPHATIDYLINOSITOL PHOSPHATIDYLCHOLINE TRANSFER PROTEINSSPECIFICALLY DEFECTIVE IN PHOSPHATIDYLINOSITOL TRANSFER - IMPLICATIONS FOR THE REGULATION OF PHOSPHOLIPID TRANSFER ACTIVITY
Jg. Alb et al., MUTANT RAT PHOSPHATIDYLINOSITOL PHOSPHATIDYLCHOLINE TRANSFER PROTEINSSPECIFICALLY DEFECTIVE IN PHOSPHATIDYLINOSITOL TRANSFER - IMPLICATIONS FOR THE REGULATION OF PHOSPHOLIPID TRANSFER ACTIVITY, Proceedings of the National Academy of Sciences of the United Statesof America, 92(19), 1995, pp. 8826-8830
The mammalian phosphatidylinositol/phosphatidylcholine transfer protei
ns (PI-TPs) catalyze exchange of phosphatidylinositol (PI) or phosphat
idylcholine (PC) between membrane bilayers in vitro, We find that Ser-
25, Thr-59, Pro-78, and Glu-248 make up a set of rat (r) PI-TP residue
s, substitution of which effected a dramatic reduction in the relative
specific activity for PI transfer activity without significant effect
on PC transfer activity, Thr-59 was of particular interest as it is a
conserved residue in a highly conserved consensus protein kinase C ph
osphorylation motif in metazoan PI-TPs, Replacement of Thr-59 with Ser
, Gin, Val, Ile, Asn, Asp, or Glu effectively abolished PI transfer ca
pability but was essentially silent with respect to PC transfer activi
ty, These findings identify rPI-TP residues that likely cooperate to f
orm a PI head-group binding/recognition site or that lie adjacent to s
uch a site, Finally, the selective sensitivity of the PI transfer acti
vity of rPI-TP to alteration of Thr-59 suggests a mechanism for in viv
o regulation of rPI-TP activity.