Cells respond to extracellular signals produced by other cells or by themselves. This mechanism, called cell signaling, allows cell-cell communication and is necessary for the functional regulation and integration of multicellular organisms. Our discussion in this chapter not only provides the basis for understanding normal cell function but serves also as an introduction tothe role of abnormal cell signaling in human disease. Signaling molecules are either secreted or expressed at the cell surface of one cell. Signaling molecules can bind to receptors on the surface of another cell or the same cell. Different types of signaling molecules transmit information in multicellular organisms, and their mechanisms of action on their target cells can be diverse. Some signalingmolecules can act on the cell surface after binding to cell surface receptors; others can cross the plasma membrane and bind to intracellular receptors in the cytoplasm and nucleus. When a signaling molecule binds to its receptor, it initiates a cascade of intracellular reactions to regulate critical functions such as cell proliferation, differentiation, movement, metabolism, and behavior.Because of their critical role in the control of normal cell growth and differentiation, signaling molecules have acquired signiﬁcant relevance in cancer research.
Cell signaling mechanisms
Box 3-A | Paracrine cell signaling
• Paracrine signaling molecules include four major families of proteins: 1. The ﬁbroblast growth factor (FGF) family. 2. The Hedgehog family. 3. The wingless (Wnt) family. 4.The transforming growth factor β (TGF-β) superfamily. • Each of these signaling proteins can bind to one or more receptors. Mutations of genes encoding these proteins may lead to abnormal cell-cell interaction. • The ﬁrst member of the Hedgehog family was isolated in a Drosophila mutant with bristles in a naked area in the normal ﬂy. The most widely found hedgehog homolog in vertebrates is sonichedgehog (Shh). Shh participates in the development of the neural plate and neural tube (see Chapter 8, Nervous Tissue). Shh binds to a transmembrane protein encoded by the patched gene and suppresses transcription of genes encoding members of the Wnt and TGF-β families and inhibits cell growth. Mutation of the patched homolog in humans (PTC) causes the Gorlin syndrome (rib abnormalities, cyst ofthe jaw, and basal cell carcinoma, a form of skin cancer). • The Wnt family of genes is named after the Drosophila gene wingless. In vertebrates, Wnt genes encode secretory glycoproteins that specify the dorsal-ventral axis and formation of brain, muscle, gonads, and kidneys. • The TGF-β superfamily encodes protein forming homodimers and heterodimers. Members of this superfamily include the TGF-βfamily itself, the bone morphogenetic protein (BMP) family, the activin family, and the vitellogenin 1 (Vg1) family. Mutations in a member of the BMP family, cartilage-derived morphogenetic protein-1 (CDMP1) causes skeletal abnormalities. Vg1 is a signaling molecule determining the left-right axis in embryos.
Five major types of cell-cell signaling are considered (Figure 3-1): 1. Endocrine cellsignaling involves a signaling molecule, called a hormone, secreted by an endocrine cell and transported through the circulation to act on distant target cells. An example is the steroid hormone testosterone produced in the testes, that stimulates the development and maintenance of the male reproductive tract. 2. Paracrine cell signaling is mediated by a signaling molecule acting locally toregulate the behavior of a nearby cell. An example is the action of neurotransmitters produced by nerve cells and released at a synapse. See Box 3-A for a summary of the four major families of paracrine signaling molecules. 3. Autocrine cell signaling is deﬁned by cells responding to signaling molecules that they themselves produce. A classic example is the response of cells of the immune system to...