Receptor tyrosine kinase family

The neurotrophin receptor p75 was first identified as a nerve growth factor (NGF)-binding protein and was subsequently shown to interact with each of the other neurotrophic factors, BDNF, neurotrophin-3, and neurotrophin-4/-5. It also modulates the activity of several members of the tropomyosin-related receptor tyrosine kinase family (Trk) (reviewed in Chao, 2003). p75, a member of the tumor necrosis factor superfamily, is a type I transmembrane protein with four cysteine-rich domains in its extracellular region and a Death domain in its cytoplasmic protein (Fig. 11). 

Pandey, A., Volkots, D. L., Seroogy, J. M. etal. Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family. J. Med. Chem. 2002, 45, 3772-3793. 

Cockerill, G.S. Lackey Karen, E. Small molecule inhibitors of the class 1 receptor tyrosine kinase family. Curr. Top. Med. Chem., 2, 1001-1010 (2002)... 

N. Y. Goldfarb, M. Yancopoulos, G.D. Identification of full-length and truncated forms of Ehk-3, a novel member of the Eph receptor tyrosine kinase family. Oncogene, 10, 1573-1580 (1995)... 

Shrivastava A, Radziejewski C, Campbell E, Kovac L, McGlynn M, RyanTE, Davis S, Goldfarb MI Glass DJ, Lemke G, Yancopoulos GD An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors. Mol Cell 1997 1 25-34. 

Human epidermal growth factor receptor-2 (HER-2 neu) is a member of the type 1 receptor tyrosine kinase family with domains on the cell surface, functioning as growth factor receptors. The type 1 receptor tyrosine kinase family includes the receptors HER-1 (EGFRorc-erbBl), HER-2 (c-erbB-2), HER-3 (c-erbB-3) and HER-4 (c-erbB-4). 

Ephrins are a group of membranous ligands, which function through a family of receptor tyrosine kinases (Ephs). Ephrin/Eph-mediated signaling processes are involved in morphogenetic processes taking place e.g. during the development of the nervous system or the vasculature. 

Growth factor family Receptor tyrosine kinase Major physiological functions... 

Besides the cytokine receptors that lack intrinsic kinase activity but have associated JAK kinases, STAT proteins can be activated by a variety of G-protein coupled receptors and growth factor receptors with intrinsic tyrosine kinase activity (for example EGF, PDGF, CSF-1, and angiotensin receptor). Increasing evidence suggests a critical role for STAT family members in oncogenesis and aberrant cell proliferation. Constitutively activated STATs have been found in many transformed cell lines and a wide variety of human tumor entities. Numerous non-receptor tyrosine kinases and viral oncoproteins, such as v-Src, v-Abl, v-Sis, and v-Eyk, have been identified to induce DNA-binding activity of STAT proteins. 

Tyrosine kinase inhibitors interfere with the function of tyrosine kinases that catalyze the transfer of the y-phosphate group of ATP to tyrosine residues of protein substrates. Tyrosine kinases can be subdivided into two large families, receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (NRTKs see corresponding chapter). The human genome... 

Many non-receptor tyrosine kinases have been identified as products of retrovirally encoded oncogenes. Non-receptor tyrosine kinases can be divided into two groups transmembrane and cytosolic families. The c-src tyrosine kinase is the prototype of the cytosolic tyrosine kinases. Regions within these non-receptor tyrosine kinases share homology with the Src kinase, known as Src homology 2 and 3 (SH2 and SH3) domains, and mediate protein-protein interactions between the receptor tyrosine kinases and the intracellular targets (reviewed in Cantley et al., 1991 Pawson and Gish, 1992 Mayer and Baltimore, 1993). 

Which of the following is classified as belonging to the tyrosine kinase family of receptors ... 

Multiple interactions are also being demonstrated between the traditional second-messenger pathways and the MAPK cascades. Free (3y G protein subunits, generated upon activation of receptors coupled to the G family, lead to activation of the ERK pathway. The mechanism by which this occurs, which may involve an interaction between the subunits and Ras or Raf, is a subject of intensive research (see Ch. 19). In addition, increases in cellular Ca2+ concentrations lead to stimulation of the ERK pathway, apparently via phosphorylation by CaMKs of proteins, for example She and Grb, that link growth factor receptor tyrosine kinases to Ras. Activation of the... 

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