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Specificity of Receptor Tyrosine Kinase Signaling Pathways: Lessons from Drosophila

  • Chapter
Genetic Engineering

Part of the book series: Genetic Engineering ((GEPM,volume 19))

Abstract

Receptor tyrosine kinases (RTKs) represent one family of membrane receptors that are commonly used to transduce extracellular signals received at the membrane into the nucleus. These proteins have intrinsic tyrosine kinase activity in their intracellular domains (1). Genetic and biochemical studies in Drosophila, C. elegans, Xenopus and in mammalian cells have identified a set of evolutionarily conserved transducing molecules common to all RTKs. These proteins, referred to as the “RTK signaling cassette” (2–4), include the adaptor protein Grb2 (a.k.a. Drk or Sem5), the tyrosine phosphatase SHP2 (a.k.a. Corkscrew, PTP1D, Syp or SHPTP2), the GTPase protein p21ras and its regulators Son of Sevenless (Sos) and Ras-Gap, and the kinases Ksr, Raf, MEK and MAPK (see Figure 1 for references). Because RTKs activate the same signaling cassette to transduce signals from the cell surface to the nucleus, a simplistic model has been proposed that suggests that the effects elicited by the activation of specific RTKs are specified by the array of transcription factors present in the cell. However, this view fails to explain results obtained, for example, in mammalian PC 12 cells whereby EGF and NGF, through their respective RTKs, activate the evolutionarily conserved signaling cassette to elicit different effects. In these cells, EGF triggers cell proliferation while NGF induces neunte extension. In the case of PC12 cells, the basis of specificity, proliferation versus differentiation, appears to depend on differences in the duration of MAPK activation (5–7).

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  1. Department of Genetics Harvard Medical School, Howard Hughes Medical Institute, Boston, MA, 02115, USA

    Willis Li & Norbert Perrimon

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  1. Willis Li
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  1. Brookhaven National Laboratory, Upton, New York, USA

    Jane K. Setlow

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Li, W., Perrimon, N. (1997). Specificity of Receptor Tyrosine Kinase Signaling Pathways: Lessons from Drosophila . In: Setlow, J.K. (eds) Genetic Engineering. Genetic Engineering, vol 19. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5925-2_9

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