Long-term down-regulation of EGF-dependent tyrosine kinase activity in PC12 cells
PC12 rat pheochromocytoma cells display cell surface receptors for both nerve growth factor (NGF) and epidermal growth factor (EGF), thus providing a model system with which to study their roles in the regulation of proliferation and differentiation. They have shown that treatment of the cells with NGF induces a progressive decrease (60-90%) in EGF receptors as monitored by (/sup 125/I)EGF binding and crosslinking. In the present report they determine EGF receptor levels in membranes from control and NGF-differentiated PC12 cells by monitoring EGF-receptor kinase activity. Measuring either the phosphorylation of a src-related synthetic peptide or the autophosphorylation of the receptor itself they found specific and maximal stimulation by 10 ng/ml EGF, but not by insulin, NGF, or cytochrome C, a complete dependency on Mn/sup 2 +/ ions, and higher specific activity in the presence of sodium vanadate. Alkaline treatment of the autophosphorylated receptor indicates that 75% of the /sup 32/P is associated with tyrosine residues. Membranes from NGF-differentiated cells show a decrease of 60-80% and 85-95% in the tyrosine kinase activity for exogenous substrate or receptor autophosphorylation, respectively. The possibility that the low levels of EGF-dependent tyrosine kinase activity in differentiated PC12 cells is an expression of a decrease in EGF receptor numbers and/or modulation of their catalytic activity by other kinases is under investigation.
- Research Organization:
- National Institute of Child Health and Human Development, Bethesda, MD
- OSTI ID:
- 6798941
- Report Number(s):
- CONF-8606151-; TRN: 87-010315
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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RECEPTORS
CELL MEMBRANES
EPIDERMIS
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NERVES
PHOSPHORUS 32
RATS
TRACER TECHNIQUES
TUMOR CELLS
TYROSINE
AMINO ACIDS
ANIMAL CELLS
ANIMAL TISSUES
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BETA-MINUS DECAY RADIOISOTOPES
BODY
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ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
EPITHELIUM
HYDROXY ACIDS
INTERMEDIATE MASS NUCLEI
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LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NUCLEI
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ORGANIC ACIDS
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ORGANS
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RODENTS
SKIN
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550201* - Biochemistry- Tracer Techniques