Nerve growth factor signal transduction in mature pig oligodendrocytes

A myriad of gene induction events underlie nerve growth factor (NGF)-induced differentiation of PC12 cells. To dissect the signal transduction pathways which lead to NGF actions, we have assessed the relative roles of NGF receptor, Src, Ras, and Raf activities in mediating specific gene inductions. We have used the PC12 cell line as well as sublines which inducibly express activated forms of either Src, Ras, or Raf or a dominant inhibitory form of Ras (p21N17 Ras) to study the expression of multiple NGF-inducible mRNAs. The NGF induction of NGFI-A, transin, and VGF mRNAs was mimicked by activated forms of Src, Ras, or Raf and was blocked by p21N17 Ras. The NGF induction of SCG10 mRNA was mimicked only by activated Src and Ras and was blocked by p21N17 Ras, while the induction of Thy-1 mRNA was mimicked only by activated Src and was not blocked by p21N17 Ras. The NGF induction of mRNAs for two sodium channel types was neither mimicked by any activated oncoprotein nor blocked by p21N17 Ras. From these and previous results, we suggest a model in which a linear order of NGF receptor, Src, Ras, and Raf activities is used by NGF to elicit gene inductions. These signaling components define branchpoints in the pathway to specific gene induction events, providing a mechanism for generating a host of diverse NGF actions.

Download Full-text

Selective Inhibition of the Expression of Signal Transduction Proteins by Lithium in Nerve Growth Factor-Differentiated PC12 Cells

Journal of Neurochemistry ◽

10.1046/j.1471-4159.1995.65062500.x ◽

2002 ◽

Vol 65 (6) ◽

pp. 2500-2508 ◽

Cited By ~ 24

Author(s):

Xiaohua Li ◽

Richard S. Jope

Keyword(s):

Signal Transduction ◽

Nerve Growth Factor ◽

Growth Factor ◽

Pc12 Cells ◽

Selective Inhibition ◽

Nerve Growth ◽

Differentiated Pc12 Cells ◽

Signal Transduction Proteins

Download Full-text

Nerve growth factor in neuronal development and maintenance

Journal of Experimental Biology ◽

10.1242/jeb.132.1.177 ◽

1987 ◽

Vol 132 (1) ◽

pp. 177-190

Author(s):

T. P. Misko ◽

M. J. Radeke ◽

E. M. Shooter

Keyword(s):

Signal Transduction ◽

Nerve Growth Factor ◽

Growth Factor ◽

Nerve Terminal ◽

Consensus Sequence ◽

Neuronal Cell ◽

Retrograde Transport ◽

Nerve Growth ◽

Lower Affinity ◽

Molecular Masses

One of the major roles of nerve growth factor (NGF) is to mediate the selective survival of a proportion of the developing sympathetic and sensory neurones as they innervate their particular target tissues. The underlying basis of this phenomenon is the synthesis of limited amounts of NGF in the target, its secretion around, and uptake by, the nerve terminal and its retrograde transport along axons to the neuronal cell bodies. The cascades of reactions which lead to neuronal survival and maintenance are initiated by signal transduction somewhere in this pathway. Retrograde transport and the initial signal transduction step begin when NGF binds to NGF receptors on the nerve terminal. Receptor-mediated internalization and the survival and maintenance function of NGF are mediated by the higher affinity receptors. These receptors have relative molecular masses of approx. 145,000 and are trypsin-resistant when occupied. In contrast, the larger population of lower affinity receptors have relative molecular masses of 85,000 and are rapidly degraded by trypsin. Clustering of the lower affinity receptors by a variety of agents gives them many of the characteristics of the higher affinity receptors, suggesting receptor interconversion may play a role in NGF actions. The structure of the lower affinity NGF receptor, determined by gene transfer and cloning, shows it to be a unique, heavily glycosylated protein. The extracellular domain is rich in cysteine-containing repeat units while the intracellular domain lacks the consensus sequence for an endogenous kinase activity. It is likely that the higher affinity receptor contains this protein as the NGF binding subunit together with a second protein which determines both the nature of the signal transduction mechanism and the process of internalization.

Download Full-text