| Literature References | 1. LEWIS, T.S., SHAPIRO, P.S. AND AHN, N.G.
Signal transduction through kinase cascades.
ADV.CANCER RES. 74 49-139 (1998).
2. ERREDE, B., CADE, R.M., YASHAR, B.M., KAMADA, Y., LEVIN, D.E., IRIE, K.
AND MATSUMOTO, K.
Dynamics and organization of MAP kinases signal pathways.
MOL.REPROD.DEV. 42 477-485 (1995).
3. HAN, J., LEE, J-D., BIBBS, L. AND ULEVITCH, R.J.
A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells.
SCIENCE 265 808-811 (1994).
4. LEE, J.C., LAYDON, J.T., MCDONNELL, P.C., GALLAGHER, T.F., KUMAR, S.,
GREEN, D., MCNULTY, D., BLUMENTHAL, M.J., HEYS, J.R., ET AL.
A protein kinase involved in the regulation of inflammatory cytokine
biosynthesis.
NATURE 372 739-746 (1994).
5. ROUSE, J., COHEN, P., TRIGON, S., MORANGE, M., ALONSO-LLAMAZARES, A.,
ZAMANILLO, D., HUNT, T. AND NEBREDA, A.R.
A novel kinase cascade triggered by stress and heat shock that stimulates
MAPKAP kinase-2 and phosphorylation of the small heat shock proteins.
CELL 78 1027-1037 (1994).
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| Documentation | MAP (Mitogen Activated Protein) kinases participate in kinase cascades,
whereby at least 3 protein kinases act in series, culminating in activation
of MAP kinase [1-2]. MAP kinases are activated by dual phosphorylation
on both tyrosine and threonine residues of a conserved TXY motif.
P38 proteins belong to the MAP kinase family and were discovered in 3
different contexts independently: first, as tyrosine phosphoproteins found
in extracts of cells treated with inflammatory cytokines [3]; second, as
targets of a pyrinidyl imidazole drug that blocks production of TNFalpha
[4]; and third, as reactivating kinases for MAP kinase-activated protein
(MAPKAP) [5]. The proteins are activated by cytokines, hormones, GPCRs,
osmotic shock, heat shock and other stresses.
P38MAPKINASE is a 5-element fingerprint that provides a signature for the
p38 MAP kinases. The fingerprint was derived from an initial alignment of 12
sequences: the motifs were drawn from regions spanning virtually the full
alignment length, focusing on those sections that characterise the p38
proteins but distinguish them from the rest of the MAP kinase family -
motif 1 includes beta-strand 2; motif 2 includes the C-terminus of helix 6;
motif 3 spans helix 11 and the N-terminus of helix 12; motif 4 encodes the
C-terminus of helix 12; and motif 5 includes helix 14. Two iterations on
SPTR40_20f were required to reach convergence, at which point a true set
comprising 23 sequences was identified. Several partial matches were also
found: MK13_PANTR and Q9D0M4 are p38 proteins from chimp and mouse that
fail to match motif 1; the rest are hypothetical proteins or closely
related MAP kinases that match 2 or 3 motifs.
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