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Sci. STKE, 21 December 1999
Vol. 1999, Issue 13, p. tw4
[DOI: 10.1126/stke.1999.13.tw4]


Pathway Crosstalk Protein Kinase A Keeps MAP Kinase from the Nucleus

Many growth factor-stimulated signaling pathways activate MAP kinases and induce their translocation to the nucleus to affect transcription. Protein tyrosine phosphatases (PTPs) have emerged as MAP kinase regulators based on their interaction with the MAP kinases p38 and the Erks. This interaction occurs at a domain called the kinase interaction motif (KIM), located outside of the phosphatase catalytic region. Association of Erks to the KIM of PTP-SL, a brain-specific protein tyrosine phosphatase, is known to retain Erks in the cytoplasm and inactivate them. Blanco-Aparicio et al. report that protein kinase A (PKA) phosphorylates a serine residue in the KIM region of PTP-SL in vitro and in vivo in transfected cells. This modification abrogated the association of PTP-SL with Erks and p38 and allowed the MAP kinases to localize to the nucleus. Phosphatase activity of PTP-SL was not required for this interaction. Similarly, Saxena et al. reported that hematopoietic PTP (HePTP) interaction with Erks was also abolished when the analagous serine residue was phosphorylated by PKA. It is possible that certain cell types have a pool of inactive MAP kinases outside the nucleus that are in a complex with these PTPs. Dissociation could occur upon activation of a cAMP-PKA pathway.

Blanco-Aparicioa, C., Torresa, J., and Pulido, R. (1999) A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase. J. Cell Biol. 147: 1129-1136. [Abstract] [Full Text]

Saxena, M., Williams, S., Taskén, K., and Mustelin, T. (1999) Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase. Nature Cell Biol. 1: 305-311. [Online Journal]

Citation: Protein Kinase A Keeps MAP Kinase from the Nucleus. Sci. STKE 1999, tw4 (1999).

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