Transforming growth factor-beta 1 regulation of signal transduction in two renal epithelial cell lines.
The present studies examine the effect of transforming growth factor-beta 1 (TGF-beta 1) on signal transduction pathways in two cultured renal epithelial cell lines. TGF-beta 1 promotes basal and agonist-stimulated adenylate cyclase activity in LLC-PK1 but not MDCK cell membranes. TGF-beta 1 stimulation of LLC-PK1 membrane adenylate cyclase activity occurs quickly and can be attenuated by pertussis toxin pretreatment. Both TGF-beta 1 and adenosine 3',5'-cyclic monophosphate (cAMP) exert comparable effects on [3H]thymidine uptake in LLC-PK1 cells, suggesting that TGF-beta 1 regulation of adenylate cyclase activity potentially plays a role in mediating biological responses to TGF-beta 1. The activities of protein kinase C and phospholipase A are not affected by TGF-beta 1 in either LLC-PK1 or MDCK cells. Both TGF-beta 1 and epidermal growth factor (EGF) increase expression and induce the appearance of new forms of the cAMP response element binding protein (CREB) in LLC-PK1 cells. These effects of TGF-beta 1 and EGF on CREB appear to be specific since neither TGF-beta 1 nor EGF alters expression of an activating transcription factor in LLC-PK1 cells. The effect of TGF-beta 1 and EGF to alter expression of CREB does not affect CREB binding to its regulatory element in LLC-PK1 cell lysates. These results suggest that some of the biological effects of TGF-beta 1 may be attributed to stimulation of adenylate cyclase activity and cAMP formation as well as to enhanced expression and/or modification of the CREB transcription factor in LLC-PK1 cells.
Anderson
R J
RJ
Department of Medicine, Denver Veterans Affairs Medical Center, Colorado.
Sponsel
H T
HT
Breckon
R
R
Marcell
T
T
Hoeffler
J P
JP
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001127:Arginine Vasopressin / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013936:Thymidine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D016212:Transforming Growth Factor beta / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D017362:Cyclic AMP Response Element-Binding Protein; D016212:Transforming Growth Factor beta; D010566:Virulence Factors, Bordetella; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D013936:Thymidine