Signaling Mechanisms in Growth Factor‐Stimulated Cell Motility
- 1 July 1997
- journal article
- review article
- Published by Oxford University Press (OUP) in The International Journal of Cell Cloning
- Vol. 15 (4), 259-267
- https://doi.org/10.1002/stem.150259
Abstract
Most mammalian cells have the capacity to migrate. When placed into culture, cells will generally display a set rate of basal, unstimulated locomotion. The cells will begin to move in one direction and, after some time, change directions resulting in a random walk. External stimuli can influence cell motility in several ways to either enhance or retard the rate of migration (chemokinesis), to change the average amount of cell migration observed before the cell turns (persistence), or to increase the directionality of movement by limiting the number of turns made by the cells. Several factors have been identified that stimulate cell movement, but the signaling mechanisms that mediate this induced cell movement have only recently begun to be studied. In this review, we discuss the signals that support the directional movement of fibroblasts and epithelial cells in response to chemoattractant gradients. The work will emphasize studies carried out by our laboratory and others on the stimulation of cell motility by the PDGF. These results indicate that at least two sets of signaling molecules cooperate to regulate cell motility in vivo. These include phospholipase C‐gamma, phosphoinositide‐3′ kinase and the Ras‐GTPase activating protein Ras‐GAP. The first set are those which bind to the intracellular domain of the receptor tyrosine kinase and bring about the phosphorylation and/or activation of intracellular effectors proximal to the receptor. The second is a set of downstream effectors that regulate either the rate of cell movement or the directionality of that movement depending on the cell type. These include Ras and the Ras‐related GTPase Rac along with free phosphoinositides and calcium ions that regulate the actin polymerization machinery. Signals that mediate nuclear changes leading to cell proliferation, such as elements of the MAP kinase pathway, do not appear to play a role in PDGF‐stimulated cell migration. Current work thus suggests that a coordinated spatial regulation of signaling elements that interact with the cell membrane and cytoskeleton but not necessarily with nuclear elements is the controlling mediator of directional cell motility.Keywords
This publication has 103 references indexed in Scilit:
- Impairment of Mobility in Endodermal Cells by FAK DeficiencyExperimental Cell Research, 1996
- Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor.JCI Insight, 1995
- The chemotactic response to PDGF-BB: evidence of a role for Ras.The Journal of cell biology, 1995
- Differential Effects of Platelet-derived Growth Factor BB on p125 Focal Adhesion Kinase and Paxillin Tyrosine Phosphorylation and on Cell Migration in Rabbit Aortic Vascular Smooth Muscle Cells and Swiss 3T3 FibroblastsPublished by Elsevier BV ,1995
- Epidermal growth factor receptor-mediated cell motility: phospholipase C activity is required, but mitogen-activated protein kinase activity is not sufficient for induced cell movement.The Journal of cell biology, 1994
- The Machinery of Cell CrawlingScientific American, 1994
- Phosphatidylinositol-3-OH kinase direct target of RasNature, 1994
- The pathogenesis of atherosclerosis: a perspective for the 1990sNature, 1993
- Interleukin (IL)-8-induced in vitro human lymphocyte migration is inhibited by cholera and pertussis toxins and inhibitors of protein kinase CBiochemical and Biophysical Research Communications, 1990
- Differential effects of the various isoforms of platelet-derived growth factor on chemotaxis of fibroblasts, monocytes, and granulocytes.JCI Insight, 1990