Two kinase sensors (reporters) have been developed to detect FGFR activity based

Question

Two kinase sensors (reporters) have been developed to detect FGFR activity based on FRET generation, and their domain structures are shown below. Both sensors have been confirmed to be highly specific for FGFR (i.e., no other kinases can activate either sensor). When the sensors are expressed in cells, stimulation of the cells with FGF leads to the two activation profiles shown below. Which sensor is more likely to report true FGFR activation profile in the cell? What elements in the sensors may have contributed to the observed difference (and how)?

Explanation / Answer

Answer a. Sensor 2 is likely to report the true FGFR activation profile in the cell.

Justification: The FRET method detects the activation of FGFR after FGF stimulation. Once complete FGFR activation takes place, the curve should get saturated which is shown in case of Sensor 2.

Answer b. SH2(b)

SH2(b) is an adaptor protein that specifically activates JAK2 and initiates receptor tyrosine kinase pathway signaling. Proteins containing SH2 domains allow docking of phosphorylated tyrosine residues on other proteins.

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