Rj. Anderson et al., TRANSFORMING GROWTH-FACTOR-BETA-1 REGULATION OF SIGNAL-TRANSDUCTION IN 2 RENAL EPITHELIAL-CELL LINES, The American journal of physiology, 265(4), 1993, pp. 60000584-60000591
The present studies examine the effect of transforming growth factor-b
eta1 (TGF-beta1) on signal transduction pathways in two cultured renal
epithelial cell lines. TGF-beta1 promotes basal and agonist-stimulate
d adenylate cyclase activity in LLC-PK1 but not MDCK cell membranes. T
GF-beta1 stimulation of LLC-PK1 membrane adenylate cyclase activity oc
curs quickly and can be attenuated by pertussis toxin pretreatment. Bo
th TGF-beta1 and adenosine 3',5'-cyclic monophosphate (cAMP) exert com
parable effects on [H-3]thymidine uptake in LLC-PK, cells, suggesting
that TGF-beta1 regulation of adenylate cyclase activity potentially pl
ays a role in mediating biological responses to TGF-beta1. The activit
ies of protein kinase C and phospholipase A are not affected by TGF-be
ta1 in either LLC-PK1 or MDCK cells. Both TGF-beta1 and epidermal grow
th factor (EGF) increase expression and induce the appearance of new f
orms of the cAMP response element binding protein (CREB) in LLC-PK1 ce
lls. These effects of TGF-beta1 and EGF on CREB appear to be specific
since neither TGF-beta1 nor EGF alters expression of an activating tra
nscription factor in LLC-PK1 cells. The effect of TGF-beta1 and EGF to
alter expression of CREB does not affect CREB binding to its regulato
ry element in LLC-PK1 cell lysates. These results suggest that some of
the biological effects of TGF-beta1 may be attributed to stimulation
of adenylate cyclase activity and cAMP formation as well as to enhance
d expression and/or modification of the CREB transcription factor in L
LC-PK1 cells.