Acidic proteins with an approximate molecular mass of 80 kD are prominent substrates for
calcium-ion/phospholipid-dependent protein kinase (protein kinase C). Sakai et al. (1989) cloned the 80K-H protein and assigned it to human chromosome 19. Partial amino acid
sequence of the 80K-L protein showed high homology with MARCKS, a phosphorylated protein of cattle. Hartwig et al. (1992) reported that MARCKS is a filamentous actin crosslinking protein, with activity that is inhibited
by PKC-mediated phosphorylation and by binding to calcium-calmodulin. MARCKS may be a regulated crossbridge
between actin and the plasma membrane, and modulation of the actin crosslinking activity of the MARCKS protein by
calmodulin and phosphorylation represents a potential convergence of the calcium-calmodulin and protein kinase C
signal transduction pathways in the regulation of the actin cytoskeleton.
NCBI Summary:
The protein encoded by this gene is a substrate for protein kinase C. It is localized to the plasma membrane and is an actin filament crosslinking protein. Phosphorylation by protein kinase C or binding to calcium-calmodulin inhibits its association with actin and with the plasma membrane, leading to its presence in the cytoplasm. The protein is thought to be involved in cell motility, phagocytosis, membrane trafficking and mitogenesis.
General function
Cytoskeleton, Actin binding
Comment
Exocytosis of oxytocin involves transport of granules through a cytoskeletal matrix including an actin cortex closely
associated with the plasma membrane (PM). Actin filaments crosslinked by various proteins give rise to the structural
integrity of the cortex. Myristoylated alanine-rich C kinase substrate (MARCKS), a protein specifically phosphorylated
by protein kinase C (PKC), crosslinks actin filaments and anchors the actin network to the inner leaflet of the PM. There
is evidence that the intact actin cortex may serve as a barrier, precluding fusion of transport vesicles with the PM. In
some secretory cells, phosphorylation of MARCKS has resulted in its translocation from the PM to the cytoplasm with
an associated disassembly of the actin cortex.
Cellular localization
Cytoplasmic, Plasma membrane
Comment
Ovarian function
Luteinization
Comment
Filley S, et al 2000 reported that phosphorylation of myristoylated alanine-rich C kinase substrate
(MARCKS) protein is associated with bovine luteal oxytocin
exocytosis.
The ruminant corpus luteum, in addition to producing progesterone, synthesizes
and secretes oxytocin (OT) during the estrous cycle. Secretion of oxytocin occurs
by exocytosis of membrane-encapsulated granules of this hormone. Exocytosis of
oxytocin involves transport of granules through a cytoskeletal matrix including an
actin cortex closely associated with the plasma membrane (PM). Actin filaments
crosslinked by various proteins give rise to the structural integrity of the cortex.
Myristoylated alanine-rich C kinase substrate (MARCKS), a protein specifically
phosphorylated by protein kinase C (PKC), crosslinks actin filaments and anchors
the actin network to the inner leaflet of the PM. In some secretory cells, phosphorylation of MARCKS has resulted in its
translocation from the PM to the cytoplasm with an associated disassembly of the
actin cortex. Prostaglandin F(2alpha) (PGF(2alpha)) stimulation of the bovine
corpus luteum during the midluteal phase of the estrous cycle activates PKC,
which is associated with an increase in OT secretion in vivo and in vitro. Data
are presented demonstrating that stimulation of bovine luteal cells with
PGF(2alpha) on Day 8 of the cycle promotes rapid phosphorylation of MARCKS
protein and causes its translocation from the PM to the cytoplasm and
concomitant, enhanced exocytosis of OT.
Expression regulated by
Comment
Ovarian localization
Oocyte, Luteal cells
Comment
Phosphorylated MARCKS: A novel centrosome component that also defines a peripheral subdomain of the cortical actin cap in mouse eggsMichaut MA, et al .
MARCKS (myristoylated alanine-rich C-kinase substrate) is a major substrate for protein kinase C (PKC), a kinase that has multiple functions during oocyte maturation and egg activation, for example, spindle function and cytoskeleton reorganization. We examined temporal and spatial changes in p-MARCKS localization during maturation of mouse oocytes and found that p-MARCKS is a novel centrosome component based its co-localization with pericentrin and gamma-tubulin within microtubule organizing centers (MTOCs). Like pericentrin, p-MARCKS staining at the MI spindle poles was asymmetric. Based on this asymmetry, we found that one end of the spindle was preferentially extruded with the first polar body. At MII, however, the spindle poles had symmetrical p-MARCKS staining. p-MARCKS also was enriched in the periphery of the actin cap overlying the MI or MII spindle to form a ring-shaped subdomain. Because phosphorylation of MARCKS modulates its actin crosslinking function, this localization suggests p-MARCKS functions as part of the contractile apparatus during polar body emission. Our finding that an activator of conventional and novel PKC isoforms did not increase the amount of p-MARCKS suggested that an atypical isoform was responsible for MARCKS phosphorylation. Consistent with this idea, immunostaining revealed that the staining patterns of p-MARCKS and the active form of the atypical PKC zeta/lambda isoform(s) were very similar. These results show that p-MARCKS is a novel centrosome component and also defines a previously unrecognized subdomain of the actin cap overlying the spindle.
Follicle stages
Corpus luteum
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: embryonic lethal Comment: To evaluate a possible
developmental role for MARCKS, Stumpo et al. (1995) disrupted its gene in mice by homologous recombination in
embryonic stem cells. Pups homozygous for the disrupted allele lacked detectable MARCKS mRNA and protein. All
MARCKS-deficient pups died before or within a few hours of birth.