Protein Tyrosine Kinase Growth Factor Receptors and their Ligands in Development, Differentiation, and Cancer

Abstract

Publisher Summary The protein tyrosine kinases (PTKs) are a thematic protein family––built around a highly conserved domain capable of phosphorylating protein substrates on tyrosine residues. Members of this family are made up as a mosaic of sensory, regulatory, and effector domains. Members of the receptor tyrosine kinases (RTK) family hold a number of structural features, such as an extracellular ligand-binding domain, a single transmembrane domain, a single protein tyrosine kinase domain, and one regulatory domain, which serves to reign in the catalytic activity of the PTK domain. This chapter discusses the structure of RTK, its developmental mutants, and tumorigenesis. The expression patterns of many human, murine, and Drosophila RTKs have been determined by Northern analysis of mRNAs from adult tissues. RTKs have been detected at elevated levels in particular types of tumor. RTKs may be overexpressed or inappropriately expressed in a ligand-independent activated form to transform cells. The chapter also reviews several aspects of the oncogenicity of members of the RTK family and the signal transduction pathways downstream of the activated receptor. The structural alterations associated with the acquisition of oncogenicity by members of RTK class of proteins are also focused in the chapter.