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Suppose you go into your lab and engineer a chimeric Ras protein in which the N-

ID: 65376 • Letter: S

Question

Suppose you go into your lab and engineer a chimeric Ras protein in which the N-terminal 20 amino acids of Ras are removed and replaced by the N-terminal 20 amino acids of insulin. What is the final destination to which this protein will be trafficked if expressed in a mouse pancreatic cell? (a) cytoplasm; (b) extracellular fluid; (c) nucleus; (d) ER lumen; (e) late endosome; (f) cell surface (intgegral to the plasma membrane).

To recap, your chimeric Ras protein has its N-terminal 20 amino acids from insulin and the remainder of its amino acid sequence from Ras. Your annoying scientific arch-rival from another university publishes a “letter to the editor” predicting this chimeric protein will localize to the inner face of the plasma membrane because it still has the C-terminal CAAX motif of Ras, which he claims will be recognized and lipid-modified by farnesyl:protein transferase in the cytoplasm. Write a brief rebuttal letter in which you use your knowledge of cell biology to puncture his postulate.

Explanation / Answer

The final destination of the to which protein will be trafficked expressed in mouse pancreatic cell is

option F ; cell surface .

2. Rebuttal letter ;

RAS is attached to cell memberane owing its prenylation and palmotylation or a combination of the perynylation and polybasic sequence to the adjacent to pernylation site .The C terminal of the caaX box gets farnysylated at its cys residue in the cytosol .allowing the Ras to loosly insert into the memberane of the ER and other cell memberanes .when activated ras propagates multiple signal transduction cascades and induces the cell poliferation ,differentiation and apoptosis . these ras proteins will undergo post translational modifications the modification include proteolytic cleavage of the CAAX box, farnelysation and palmitylation which act as a plasma memberane anchors ,where most signal transductions takes place .In CAAX box , C represents the cysteine , AA represent the aliphatic aminoacid , X any amino acid . the farnesyl is added to terminal cysteine tat newly exposed carboxy terminus . So these proteins thereby stable memberane and are transported to the plasma memberane on vesicle of secretory pathway .

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