Affiliation:
1. Department
of Cell Biology, Harvard Medical School, Boston, Massachusetts
02115
Abstract
SUMMARY
Conserved signaling pathways that activate the mitogen-activated
protein kinases (MAPKs) are involved in relaying extracellular
stimulations to intracellular responses. The MAPKs
coordinately regulate cell proliferation, differentiation, motility,
and survival, which are functions also known to be mediated by members
of a growing family of MAPK-activated protein kinases (MKs;
formerly known as MAPKAP kinases). The MKs are related
serine/threonine kinases that respond to mitogenic and stress stimuli
through proline-directed
phosphorylation and activation of
the kinase domain by extracellular signal-regulated kinases 1 and 2 and
p38 MAPKs. There are currently 11 vertebrate MKs in five
subfamilies based on primary sequence homology: the ribosomal S6
kinases, the mitogen- and stress-activated kinases, the
MAPK-interacting kinases, MAPK-activated protein
kinases 2 and 3, and MK5. In the last 5 years, several MK substrates
have been identified, which has helped tremendously to identify the
biological role of the members of this family. Together with data from
the study of MK-knockout mice, the identities of the MK substrates
indicate that they play important roles in diverse biological
processes, including mRNA translation, cell proliferation and
survival, and the nuclear genomic response to mitogens and cellular
stresses. In this article, we review the existing data on the MKs and
discuss their physiological functions based on recent
discoveries.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology,Infectious Diseases
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