Receptors, Signaling Pathways, Cell Cycle, and DNA Damage Repair

Abstract

Ligands are extracellular messenger molecules such as growth factors, inflammatory cytokines, and hormones that bind to specific receptors on the cell surface (i.e., growth factor receptors, cytokine receptors, and hormone receptors). Binding of the ligands to their receptors causes activation of second messengers in the cytosol and, eventually, activation of nuclear transcription factors. (Transcription factors are discussed in Chap. 1) The transcription factors then direct the transcription of a gene product as a result of the extracellular message (e.g., a growth factor may stimulate a growth factor receptor on the cell surface, causing activation of second messengers that eventually cause a transcription factor to cause transcription of a protein involved in cell growth). This cascade or activation and inactivation of protein messengers from the cell-surface receptors through proteins in the cytosol to the transcription factors in the nucleus is known as signal transduction. The series of steps that occurs during this process is called the signal transduction pathway or signaling pathway. Much of the activation and inactivation of proteins in signaling pathways occurs through reversible phosphorylation of tyrosine, serine, or threonine in the pathway proteins (see Chap. 1). Phosphorylation is accomplished by tyrosine kinases and serine/threonine kinases with phosphates donated from adenosine triphosphate (ATP) or guanosine triphosphate (GTP). Tyrosine kinases are much more common in signaling pathways than are serine/threonine kinases.1-10 This discussion focuses on growth factor receptors and cytokine receptors and their associated signaling pathways.