Angiotensin II activates mitogen-activated protein kinase via protein kinase C and Ras/Raf-1 kinase in bovine adrenal glomerulosa cells

Endocrinology. 1998 Apr;139(4):1801-9. doi: 10.1210/endo.139.4.5865.


Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal glomerulosa cells, but little is known about the signaling pathways that mediate these responses. An analysis of the growth-promoting pathways in cultured bovine adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor, caused rapid but transient activation of mitogen-activated protein kinase (MAPK), with an ED50 of 10-50 pM. Although neither Ca2+ influx nor Ca2+ release from intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a permissive role in this response. A major component of Ang II-induced MAPK activation was insensitive to pertussis toxin (PTX), although a minor PTX-sensitive component could not be excluded. Ang II also induced the rapid activation of ras and raf-1 kinase with time-courses that correlated with that of MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II-induced MAPK activation. Ang II also stimulated a mobility shift of raf-1, reflecting hyperphosphorylation of the kinase. However, unlike its activation, raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated not with activation, but rather with deactivation of the kinase. Taken together, these findings indicate that Ang II stimulates multiple pathways to MAPK activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cattle
  • Egtazic Acid / pharmacology
  • Enzyme Activation / drug effects
  • Kinetics
  • Pertussis Toxin
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Proto-Oncogene Proteins c-raf / metabolism*
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Angiotensin / physiology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Virulence Factors, Bordetella / pharmacology
  • Zona Glomerulosa / enzymology*
  • ras Proteins / metabolism*


  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Angiotensin
  • Virulence Factors, Bordetella
  • Angiotensin II
  • Egtazic Acid
  • Pertussis Toxin
  • Proto-Oncogene Proteins c-raf
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • ras Proteins
  • Tetradecanoylphorbol Acetate
  • Calcium