Question

Growth factor signaling through receptor tyrosine kinases (RTKs) results in multiple phenotypic changes. These changes are elicited in part by RTK activation of distinct yet specific intracellular signaling pathways. Describe the mechanism whereby a growth factor leads to the activation of several different yet specific pathways, and how that specificity is achieved. Begin with the growth factor and end with activation of the different intracellular signaling pathways. You must be comprehensive in your answer. Answer in no more than six sentences.

Answer 1

Cellular responses to growth factors are mediated by tyrosine kinases (RTKs)1 cell surface receptor which have an intrinsic activity of tyrosine kinase protein.Growth factor binding induces dimerisation of receptors and autophosphorylation of several tyrosine residues, and phosphorylated tyrosines provide docking sites for intracellular signaling proteins containing Src homology 2 or protein tyrosine binding domains .

The sequence-specific recruitment of pairs of signing proteins triggered RTKs to intracellular signaling cascades that spread signals to the nucleus to induce initial gene expression changesGrowth factor-stimulated expression of immediate early genes (IEGs), or genes whose activation does not require protein synthesis, lays the foundation for cellular ultimate response.

Several signaling cascades linking activated RTKs to the nucleus were characterized during the past decade.Activation of the Erk serine / threonine kinases, for example, follows the recruitment of the Grb2/SOS complex to receptors and the Ras GTPase stimulus.Erk phosphorylation of ternary complex factors leads to the stimulation of genes in their promoters which contain serum response elements.

Activation of phosphoinositide 3′-kinase (PI3 K) growth factors leads to fork phosphorylation and CREB transcription factors by stimulating the serine / threonine kinase cycle and triggering the nuclear factor £ B by regulating the I£B kinase mechanism.