Growth Factors: Protein Processing, Endocytosis, and Intracellular Sorting

Abstract

Growth factor (GF) receptors are extracellular receptors which, when bound by growth factors, initiate intracellular signaling for promoting cellular proliferation, survival, and differentiation. The amount of signaling is generally controlled by both the levels of growth factor and the levels of GF receptors present in the cell, particularly at the cell surface. This review will focus on the mechanisms of endocytosis and postendocytic trafficking that serve to control the levels of GF receptors. The classical experimental system used to investigate these processes is the endocytosis of GF receptors that possess intrinsic tyrosine kinase activity, known as receptor tyrosine kinases (RTKs). We will use the prototypical RTK, epidermal growth factor receptor (EGFR), as the model GF receptor in this discussion since much of the data leading to the current understanding of GF receptor endocytosis was generated using this receptor.Growth factor (GF) receptors are extracellular receptors which, when bound by growth factors, initiate intracellular signaling for promoting cellular proliferation, survival, and differentiation. The amount of signaling is generally controlled by both the levels of growth factor and the levels of GF receptors present in the cell, particularly at the cell surface. This review will focus on the mechanisms of endocytosis and postendocytic trafficking that serve to control the levels of GF receptors. The classical experimental system used to investigate these processes is the endocytosis of GF receptors that possess intrinsic tyrosine kinase activity, known as receptor tyrosine kinases (RTKs). We will use the prototypical RTK, epidermal growth factor receptor (EGFR), as the model GF receptor in this discussion since much of the data leading to the current understanding of GF receptor endocytosis was generated using this receptor.