Interference No. 104,436 Paper 98
Shyamala v. Hillman Page I I
[781 According to McLaughlin, inhibition of p38 could block certain inflammatory processes and "has
been implicated in the apoptosis of neurons upon growth factor removal" [ 1006 at 8488:R].
[791 Apoptosis means programmed cell death: " a cell's inherent, inducible self-destruction
mechanism.
[80] McLaughlin reports using a yeast two-hybrid screen, like Shyamala's, to identify other proteins
that interact with p38 [1006 at 8488:R].
[811 McLaughlin isolated a protein that interacted with, and appeared to be a substrate of, p38 [1006
at 8488:L].
[82] McLaughlin did not suggest a use for its protein.
[83] McLaughlin suggests that in April 1996, the search for proteins interacting with p38 was a hot
research area and that the use of yeast two-hybrid systems to conduct the search was a standard
approach to the problem.
[841 The Han article 12 [1007] waspublished in 1994.
[851 Han reports that mammalian cells phosphorylate p38 in response to lipopolysaccharide
endotoxins from Gram-negative bacteria [1007 at 808].
[86] Han also reports that p38 is also phosphorylated in response to increases in extracellular
osmolarity (1007 at 809], a type of cellular stress.
[87] Han does not indicate a practical use for p38.
[88] Han confirms that p38 was a subject of research interest.
B. Alberts et al., Molecular Biology of the Cell at G-3 (3d ed. 1994).
12 J. Han, L.-D. Lee, L. Bibbs & RJ. Ulevitch, "A MAP Kinase Targeted by Endotoxin and HyperosmoMty in
Manunalian Cells", 265 Science 808 (5 Aug. 1994) (Han). The Han authors are with the Scripps Research Institute.
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