THE DIFFERENTIAL ROLE OF PROTEIN-KINASE-C ISOZYMES IN THE RAPID INDUCTION OF NEUROFILAMENT PHOSPHORYLATION BY NERVE GROWTH-FACTOR AND PHORBOL ESTERS IN PC12 CELLS

被引:33
作者
CLARK, EA [1 ]
LEE, VMY [1 ]
机构
[1] UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,GRAD GRP CELL BIOL,PHILADELPHIA,PA 19104
关键词
NERVE GROWTH FACTOR; PROTEIN KINASE-C; NEUROFILAMENT ISOFORMS; NEUROFILAMENT PHOSPHORYLATION; PHORBOL ESTERS;
D O I
10.1111/j.1471-4159.1991.tb08222.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We examined the short-term regulation of the phosphorylation of the mid-sized neurofilament subunit (NF-M) by kinases which were activated in rat pheochromocytoma (PC12) cells by nerve growth factor (NGF) and/or 12-O-tetradecanoylphorbol 13-acetate (TPA). We found that NGF and TPA, alone or in combination, increased (a) the incorporation of [P-32]P(i) into NF-M and (b) the rate of conversion of NF-M from a poorly phosphorylated to a more highly phosphorylated form. This was due to increased synthesis of NF-M, because NGF alone did not increase NF-M synthesis and TPA alone or TPA and NGF together inhibited the synthesis of NF-M. Further, an increase in calcium/phospholipid-dependent kinase (PKC) activity resulting from the treatment of PC12 cells with NGF and TPA was observed concomitant with the increased phosphorylation of NF-M. This PKC activity was determined to be derived from the PKC-alpha and PKC-beta isozymes. Finally, when PC12 cells were rendered PKC-deficient by treatment with 1-mu-M TPA for 24 h, NGF maintained the ability to induce an increase in NF-M phosphorylation, though not to the level attained in cells which were not PKC-deficient. These data suggest that NGF with or without TPA stimulates NF-M phosphorylation as a result of a complex series of events which include PKC-independent and PKC-dependent pathways.
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页码:802 / 810
页数:9
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