Articles 
Anderson, M.P., Berger, HA., Rich, D.P., Gregory, 
R.J., Smith, A.E., and Welsh, M.J. 1991. Nucleo- 
side triphosphates are required to open the CFTR 
chloride channel. Cf// 67:775-784. 
Anderson, M.P., Sheppard, D.N., Berger, H.A., and 
Welsh, M.J. 1992. Chloride channels in the api- 
cal membrane of normal and cystic fibrosis airway 
and intestinal epithelia. Am J Physiol 263:L1- 
L14. 
Berger, H.A., Anderson, M.P., Gregory, R.J., Thomp- 
son, S., Howard, P.W., Maurer, R.A., Mulligan, R., 
Smith, A.E., and Welsh, M.J. 1991. Identification 
and regulation of the cystic fibrosis transmem- 
brane conductance regulator-generated chloride 
channel. /C/m Invest 88:1422-1431. 
Cheng, S.H., Rich, D.P., Marshall, J., Gregory, RJ., 
Welsh, M.J., and Smith, A.E. 1991. Phosphoryla- 
tion of the R domain by cAMP-dependent protein 
kinase regulates the CFTR chloride channel. Cell 
66:1027-1036. 
DeLisle, S., Pittet, D., Potter, B.V., Lew, P.D., and 
Welsh, M.J. 1992. InsPj and Ins(l ,3,4,5)P4 act 
in synergy to stimulate influx of extracellular 
Ca^^ in Xenopus oocytes. Am J Physiol 
262:C1456-C1463. 
DeLisle, S., and Welsh, M.J. 1992. Inositol tris- 
phosphate is required for the propagation of cal- 
cium waves in Xenopus oocytes. / Biol Chem 
267:7963-7966. 
Denning, G.M., Anderson, M.P., Amara, J.F., Mar- 
shall, J., Smith, A.E., and Welsh, M.J. 1992. Pro- 
cessing of mutant cystic fibrosis transmembrane 
conductance regulator is temperature-sensitive. 
Nature 358:761-764. 
Denning, G.M., Ostedgaard, L.S., Cheng, S.H., 
Smith, A.E., and Welsh, M.J. 1992. Localization 
of cystic fibrosis transmembrane conductance reg- 
ulator in chloride secretory epithelia. / Clin In- 
vest 89:339-349. 
Denning, G.M., Ostedgaard, L.S., and Welsh, 
M.J. 1992. Abnormal localization of cystic fibro- 
sis transmembrane conductance regulator in pri- 
mary cultures of cystic fibrosis airway epithelia./ 
Cell Biol 118:551-559. 
Ostedgaard, L.S., Shasby, D M., and Welsh, M.J. 
1992. Staphylococcus aureus alpha-toxin per- 
meabilizes the basolateral membrane of a CP-se- 
creting epithelium. Am J Physiol 263:L104- 
L112. 
Smith, JJ., and Welsh, M.J. 1992. cAMP stimulates 
bicarbonate secretion across normal, but not cys- 
tic fibrosis airway epithelia. / Clin Invest 
89:1148-1153. 
Tilly, B.C., Winter, M.C., Ostedgaard, L.S., O'Rior- 
dan, C, Smith, A.E., and Welsh, M.J. 1992. Cy- 
clic AMP-dependent protein kinase activation of 
cystic fibrosis transmembrane conductance regu- 
lator chloride channels in planar lipid bilayers./ 
Biol Chem 267:9470-9473. 
Welsh, M.J., Anderson, M P., Rich, D.P., Berger, 
H.A., Denning, G.M., Ostedgaard, L.S., Shep- 
pard, D.N., Cheng, S., Gregory, RJ., and Smith, 
A.E. 1992. Cystic fibrosis transmembrane con- 
ductance regulator: a chloride channel with novel 
regulation. Neuron 8:821-829. 
MOLECULAR BIOLOGY OF GROWTH FACTOR SIGNAL TRANSDUCTION 
Lewis T. Wu.liams, M.D., Ph.D., Investigator 
Dr. Williams's group previously developed an ap- 
proach to mapping sites of interaction between 
intracellular signaling molecules and receptor 
tyrosine kinases. Short tyrosine-phosphorylated 
peptides representing receptor sequences were 
used to block the binding of signaling molecules to 
the receptor in vitro and thereby identify the recep- 
tor sequence that binds each signaling molecule. 
Using this principle, the group showed that it was 
possible to inactivate an individual intracellular sig- 
naling pathway selectively by mutating the specific 
receptor tyrosine that binds the signaling molecule 
that triggers the pathway. This year these and other 
approaches were used to learn more about receptor- 
triggered interactions of signaling molecules. 
Phosphatidylinositol 3-Kinase 
Using a platelet-derived growth factor (PDGF) re- 
ceptor point mutant (Y708/719F) that was shown 
previously by Dr. Williams's group to be selectively 
defective in binding phosphatidylinositol 3-kinase 
(PI 3-kinase), they recently found that this receptor 
mutant was unable to stimulate Raf-1 and microtu- 
bule-associated protein (MAP) kinases. This mutant 
CELL BIOLOGY AND REGULATION 
119 
