Signal-transducing proteins

Wood, K. W Samecki, C., Roberts, T. M and Blenis, J. (1992). ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases MAP kinase, Raf-1, and RSK. Cell 68 1041-1050. 

Denhardt DT. Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell the potential for multiplex signalling. B/oc/jeraJ 1996 318 729-747. 

Wodicka, L. M. and Morse, D. E., cDNA sequences reveal mRNAs for two Ga signal transducing proteins from larval cilia, Biol. Bull., 180, 1991. 

Signal transducing proteins general subunit structure... 

Gedrich, R. W., Gilfillan, M. C., Duckett, C. S., Van Dongen, J. L., and Thompson, C. B. (1996). CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins./. Biol. Chem. 271, 12852-12858. 

Sato, T., Irie, S., and Reed, J. C. (1995). A novel member of the TRAP family of putative signal transducing proteins binds to the cytosolic domain of CD40. FEBS Lett. 358, 113-118. 

Cbl A signal transducing protein downstream of a number of receptors coupled... 

In addition to phosphorylating itself, the insulin receptor catalyzes the tyrosine phosphorylation of a number of specific intracellular proteins (see Figure 25-14). These include the four members of the family of insulin-receptor substrate (IRS) proteins (termed IRS-1, IRS-2, IRS-3, and IRS-4), She, and Gab-1. The phosphorylated tyrosines on these target proteins act as docking sites for selected intracellular signal transducer proteins. Most of these transducer proteins contain one or more Sre homology 2 (SH2) domains. The SH2 domain is a sequence of approximately 100 amino acids... 

Short peptide sequences containing phosphotyroslne residues are bound by SFI2 and PTB domains, which are found in many signal-transducing proteins. Such protein-protein interactions are Important in many signaling pathways. 

Genetic Studies in Drosophila Identify Key Signal-Transducing Proteins Downstream from Receptor Tyrosine Kinases... 

To identify Intracellular signal-transducing proteins in the Sev RTK pathway, investigators produced mutant flies expressing a temperature-sensitive Sev protein. When these flies were maintained at a permissive temperature, all their ommatidia contained R7 cells when they were maintained at a nonpermissive temperature, no R7 cells developed. At a par-... 

The SH2 domain in PT3 kinase binds to phosphotyro-slne residues in the cytosolic domain of many activated RTKs and cytokine receptors. The recruitment of PT3 kinase to the plasma membrane by activated receptors positions Its catalytic domain near its phospholnositide substrates on the cytosolic face of the plasma membrane, leading to formation of PI 3,4-bisphosphate or PI 3,4,5-trisphosphate (Figure 14-26). By acting as docking sites for various signal-transducing proteins, these membrane-bound PI 3-phosphates in turn transduce signals downstream In several important pathways. 

Drugs that target other signal-transducing proteins may be useful in controlling their abnormal activities. One example is Ras, which is anchored to cell membranes by farnesyl... 

The activity of Src, a cyrt osolIc signal-transducing protein-tyrosine kinase, normally is regulated by reversible phosphorylation and dephosphorylation of a tyrosine residue near the C-termlnus (see Figure 23-17). The unregulated activity of Src oncoproteins that lack this tyrosine promotes abnormal proliferation of many cells. 

Although many different signal transducer proteins have SH2 domains, and many receptors have phosphotyrosine residues, each signal transducer protein is specific for one type of receptor. This specificity of binding results from the fact that each phosphotyrosine residue has a different amino acid sequence around it that forms the binding domain. Likewise, the SH2 domain of the transducer protein is only part of its binding domain. 

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