Question

Hi, this question has 3 parts and I need help answering them

The Epidermal Growth Factor Receptor (EGFR) is a receptor tyrosine kinase that regulates cell growth. For each of the scenarios below, explain which steps of RTK signaling would act normally and which would change. Describe what effects you would expect to observe in each cell. a. An inhibitor binds to the EGFR ligand binding site but does not induce dimerization. b. The tyrosine residues on EGFR are replaced with glycine residues. c. EGFR is mutated so that pairs dimerize all the time, even when ligand is absent.

Answer 1

Answer-The epidermal growth factor receptor(EGER)is a receptor tyrosine kinase.Receptor tyrosine kinase (RTK)have intrinsic protein tyrosin kinase activity in their cytosolic domains.Ligand for RTK may be HArmone or any growth factor likr Epidermal growth factor,nerve growth factor ,fibroblast growth factor etc.

When suitable ligand bind to RTK receptor the ligand induced activation of RTK stimulates its tyrosine kinase activity ,which subsequently stimulates the Ras-MAP kinase pathway and several other signal transduction pathway,

RTK pathway- it has following steps-

1)Binding of growth factor causes dimerization and phosphorylation of cytosolic receptor tyrosine residues.

2) An SH2 domain of GRB2 binds to a phosphotyrosine residue in activated RTK.GRB2 also contains two SH3 domain which bind and activate sos thus GRB2 fuction as adaptor protein for RTK pathway.inding of GRB2 and SOS couples receptor to inactive Ras.

3) Sos promotes dissosiation of GDP from Ras,GTP binds and activtes Ras..Actie Ras dissociates from Sos and transduce signal from Raf,MEK,and MAP kinase pathway.

Figure 3.22 Activation of MITF transcription factor through the binding of stem cell factor by the Kit RTK protein (Part 2) Stem cell factor Extracellular Receptor (Kit) Cytoplasm Adaptor protein (SOs) GNRP Ras GDP ER Melanoblast- specific gene MITF MEK Ras GTP p300/CBP RAF Transcription DEVELOPMENTAL BIOLOGY, 9e, Figure 3.22 (Part 2) inauer Assocanes, Inc

Answer A) If an inhibitor binds to the EGFR ligand binding site but does not induce dimerization.The whole process of signal transduction from RTK--->Ras---->Raf----->MEK-----> MAP kinase stop.Because dimerization is most important step for the activation and signal transduction.So in this case absence of dimerization changes whole process.

c)If EGFR is mutated so that pairs dimerize all the time ,even when ligand is absent.In this case steps of RTK pathway act normally because the dimerization occur.but due to continue and excessive product formation this condion may lead some prblems and become carcinogenic.because RTK function in regulation of cell proliferation and differentiation ,promotion of cell survival and modulation of celluler metabolism.

All the process should have atight control which is require to insure normal tissue patterning

B) Glycine also produces the same effect and essential for the receptors activity there will be no change .