Role of the cAMP-dependent protein kinase and protein kinase C in regulating the morphological differentiation of PC12 cells

✍ Scribed by D. Glowacka; Dr. J. A. Wagner

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 793 KB
• Volume: 25
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490250403

✦ Synopsis

The cell line A126-1B2 is a PC12-derived mutant that is resistant to the toxic effects of dibutyryladenosine 3'5'-cyclic monophosphate (dbcAMP) and is deficient in adenosine 3':5'-cyclic monophosphate (CAMP)-dependent protein kinase I1 (PKAII). This mutant formed neurites in response to nerve growth factor (NGF), but not in response to dbcAMP; and dbcAMP did not increase the rate of NGF-dependent neurite formation. Thus, while PKAII is essential for process formation in response to agents that act through the CAMP-dependent pathway, activation of PKAII is not essential for NGF-dependent neurite formation. Unexpectedly, NGF and phorbol 12-myristate 13-acetate (PMA; 10-1,000 nM) synergistically stimulated the formation of short processes that were apparent within 30 min of NGF addition in 85% of these mutant cells. These processes were similar, but not identical, in appearance to the NGF-dependent neurites that formed only after a period of 24-48 hr. This effect is dependent on the activation of protein kinase C (PKC) because an inactive phorbol ester was without effect. In contrast, there was only a small effect of NGF and/or PMA on process formation in wild type cells within the first few hours. The effect of PMA is not augmented by dbcAMP in the A126-IB2 mutant cells. After several hours, PMA caused a concentration-dependent decrease in cell adhesion; and higher concentrations of PMA resulted in a transient detachment of the cells and a loss of neurites. These experiments suggest a role for PKC in the regulation of process formation.