Biomedical Engineering Reference
In-Depth Information
recent studies have elucidated the physiological functions of these cascades
in the control of gene expression, cell proliferation and programmed cell
death. the MapK cascade comprises distinct groups of protein kinases
which have been characterized in mammals (table 3.2).
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3.4.7 Transcription factors regulating osteoblast
differentiation
Transcription factors address the commitment of MSCs to tissue-specific
cell types, and runx2 is considered to be a master regulatory switch which
mediates the temporal activation and/or repression of genes differentiation
which is essential for osteoblast differentiation.
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other genes are required
to progress the differentiation programme, such as osx, which encodes
a transcription factor genetically 'downstream' of runx2.
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runx2 is a
member of the runx (runt-related factors) family of transcription factors.
the family members, runx1 and runx3, are encoded by distinct unlinked
genes but share a common dNa recognition motif and heterodimerize with
the ubiquitous subunit Cbfß for stable dNa binding. runx2 is abundantly
expressed in calcified cartilage and bone. The peculiarity of Runx2 is the
transactivation domain, rich in glutamine and alanine residues, which serves
Table 3.2
Familiesofmitogen-activatedproteinkinases
Family
Name
Function
Extracellular
ERK1,ERK2
TheERKs(alsoknownasclassicalMAPK)
signal-regulated
signallingpathwaysareactivatedin
kinases
responsetogrowthfactorsandregulate
cellproliferationandcelldifferentiation.
ERK5(MAPK7)
Activatedbothbygrowthfactorsandby
stressstimuli,itparticipatesincell
proliferation.
ERK3(MAPK6)
AtypicalMAPKs:ERK3/4aremostly
ERK4(MAPK4)
cytoplasmicproteinwhichbinds,
translocatesandactivatestheMK5(PRAK,
MAP2K5).ERK3isknowntobeunstable
unlikeERK4whichisrelativelystable.
ERK7/8.(MAPK15) NewmembersofMAPKsstructurally
relatedtoERK3/4.
c-JunN-terminal MAPK8,MAPK9, Stress-activatedproteinkinases
kinases(JNKs)
MAPK10
(SAPKs)
p38isoforms
MAPK11,MAPK12 BothJNKandp38signalingpathwaysare
(ERK6),MAPK13, responsivetostressstimuli,suchas
MAPK14
cytokines,ultravioletirradiation,heat
shockandosmoticshock,andare
involved in cell differentiation and
apoptosis.
