Receptor tyrosine kinase Function

Eph A family of receptor tyrosine kinases function as receptors/Ugands for ephrins... 

Figure 13.24 Six subfamilies of receptor tyrosine kinases involved in cell growth and differentiation. Only one or two members of each subfamily are indicated. Note that the tyrosine kinase domain is interrupted by a "kinase insert region" in some of the subfamilies. The functional significance of the cysteine-rich and immunoglobulin-like domains is unknown.

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... 

Insulin Receptor. Figure 1 Structure and function of the insulin receptor. Binding of insulin to the a-subunits (yellow) leads to activation of the intracellular tyrosine kinase ((3-subunit) by autophosphorylation. The insulin receptor substrates (IRS) bind via a phospho-tyrosine binding domain to phosphorylated tyrosine residues in the juxtamembrane domain of the (3-subunit. The receptor tyrosine kinase then phosphorylates specific tyrosine motifs (YMxM) within the IRS. These tyrosine phosphorylated motifs serve as docking sites for some adaptor proteins with SRC homology 2 (SH2) domains like the regulatory subunit of PI 3-kinase. 

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... 

Gronborg, M., Wulff, B. S., Rasmussen, J. S., Kjeldsen, T., and Gammeltoft, S., Structure-function relationship of the insulin-like growth factor-I receptor tyrosine kinase, J. Biol. Chem., 268, 23435-13440, 1993. 

Henderson, J. T., Georgiou, J., Jia, Z. P. et al. The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function. Neuron 32 1041-1056, 2001. 

The functions of transmembrane receptors can be modified using adaptor motecules. Sometimes the adaptors bring in substrates to the receptor s enzyme activity, but other times they can bring in the activity itsetf. The best known adaptors have protein structurai domains called SH2 or SH3 domains. These adaptors couple various functions to receptor tyrosine kinases (Fig. 9-4). SH2 and SH3 stands for Src homotogy region 2 and 3 because they were discovered first in the oncogene, Src (see tater). These adapters recognize specific phosphotyrosine residues in the autophosphorylated receptor. Src itsetf is not a receptor, but it is a tyrosine kinase. It has an SH2 and SH3 domain to tink it to the receptor and, when this occurs, it becomes activated as a tyrosine kinase. 

FUNCTION OF THE MEMBRANE BOUND ISOFORM LIGANDS OF THE RECEPTOR TYROSINE KINASE SUBCLASS III IN INDUCING SELF RENEWAL OF EARLY HEMATOPOIETIC PROGENITOR CELLS... 

Whatever the nature of the receptor tyrosine kinase subclass 111 ligand isoforms involved, it is presently unclear whether they induce different signaling effects in early hematopoietic cells upon binding to its receptor. To determine the function of the SCF/CSF-1 isoforms we used an embryonic epithelial cell line to express ectopically each membrane-bound and soluble ligand. In cocultures with human and murine early progenitor cells we determined their proliferative and developmental responses. 

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