Involvement of G proteins, cytoplasmic calcium, phospholipases, phospholipid-derived second messengers, and protein kinases in signal transduction from mitogenic cell surface receptors

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Abstract
The binding of growth factors to cell surface receptors rapidly induces a mitogenic signal transduction cascade, which results in transcriptional activation of early response genes such as fos [ 1 , 2 ]. This mitogenic signal transduction process involves a complex series of events, including tyrosine phosphorylation, Ras G-protein-dependent effects, activation of phospholipases, and activation of protein kinase C and other cytoplasmic serine/threonine protein kinases that transduce the mitogenic signal from the cell membrane to the cell nucleus. In addition to the rapid activation of fos transcription, there are rapid changes in phosphorylation of the Jun protein. The newly synthesized Fos protein complexes with newly phosphorylated Jun protein via leucine zipper motifs; this produces the active Fos:Jun heterodimer known as AP-1(Fos:Jun) [ 3 , 4 ]. AP-1(Fos:Jun) is a transcription control factor that modulates the transcription of numerous genes that contain AP-1 control elements. The activation of AP-1(Fos:Jun) in response to mitogenic stimuli occurs during the transition between the G0 phase (the resting stage of the cell cycle) and G1, phase (the stage when the cell becomes committed to undergo mitosis). This initiation of the G1 phase is followed several hours later by the activation of DNA synthesis (S phase) and eventually mitosis (M phase). This chapter focuses on the signal transduction pathways, which may connect stimulation of cell surface receptors to an important early G1 phase response, i.e., AP-1(Fos:Jun) formation via activation of fos transcription and Jun phosphorylation.

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