MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin

J. H. Hartwig; M. Thelen; A. Resen; P. A. Janmey; A. C. Nairn; A. Aderem

doi:10.1038/356618a0

MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin

J. H. Hartwig, M. Thelen, A. Resen, P. A. Janmey, A. C. Nairn, A. Aderem

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Abstract

Agonists that stimulate protein kinase C (PKC) induce profound changes in cell morphology correlating with the reorganization of submembranous actin^1,2, but no direct connection between PKC and actin assembly has been identified³. The myristoylated, alanine-rich C kinase substrate (MARCKS) binds calmodulin^4,5 and is a predominant, specific substrate of PKC which is phosphorylated during macrophage and neutrophil activation^6-8, growth factor-dependent mitogenesis^9,10and neurosecretion^11,12; it is redistributed from plasma membrane to cytoplasm when phosphorylated^13-15 and is involved in leukocyte motility^14,15. Here we report that MARCKS is a filamentous (F) 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 PKC signal transduction pathways in the regulation of the actin cytoskeleton.

Original language	English (US)
Pages (from-to)	618-622
Number of pages	5
Journal	Nature
Volume	356
Issue number	6370
DOIs	https://doi.org/10.1038/356618a0
State	Published - 1992
Externally published	Yes

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@article{cc16187ae9d941f0bb190ef5e8a56f41,

title = "MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin",

abstract = "Agonists that stimulate protein kinase C (PKC) induce profound changes in cell morphology correlating with the reorganization of submembranous actin1,2, but no direct connection between PKC and actin assembly has been identified3. The myristoylated, alanine-rich C kinase substrate (MARCKS) binds calmodulin4,5 and is a predominant, specific substrate of PKC which is phosphorylated during macrophage and neutrophil activation6-8, growth factor-dependent mitogenesis9,10and neurosecretion11,12; it is redistributed from plasma membrane to cytoplasm when phosphorylated13-15 and is involved in leukocyte motility14,15. Here we report that MARCKS is a filamentous (F) 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 PKC signal transduction pathways in the regulation of the actin cytoskeleton.",

author = "Hartwig, {J. H.} and M. Thelen and A. Resen and Janmey, {P. A.} and Nairn, {A. C.} and A. Aderem",

year = "1992",

doi = "10.1038/356618a0",

language = "English (US)",

volume = "356",

pages = "618--622",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "6370",

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TY - JOUR

T1 - MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin

AU - Hartwig, J. H.

AU - Thelen, M.

AU - Resen, A.

AU - Janmey, P. A.

AU - Nairn, A. C.

AU - Aderem, A.

PY - 1992

Y1 - 1992

N2 - Agonists that stimulate protein kinase C (PKC) induce profound changes in cell morphology correlating with the reorganization of submembranous actin1,2, but no direct connection between PKC and actin assembly has been identified3. The myristoylated, alanine-rich C kinase substrate (MARCKS) binds calmodulin4,5 and is a predominant, specific substrate of PKC which is phosphorylated during macrophage and neutrophil activation6-8, growth factor-dependent mitogenesis9,10and neurosecretion11,12; it is redistributed from plasma membrane to cytoplasm when phosphorylated13-15 and is involved in leukocyte motility14,15. Here we report that MARCKS is a filamentous (F) 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 PKC signal transduction pathways in the regulation of the actin cytoskeleton.

AB - Agonists that stimulate protein kinase C (PKC) induce profound changes in cell morphology correlating with the reorganization of submembranous actin1,2, but no direct connection between PKC and actin assembly has been identified3. The myristoylated, alanine-rich C kinase substrate (MARCKS) binds calmodulin4,5 and is a predominant, specific substrate of PKC which is phosphorylated during macrophage and neutrophil activation6-8, growth factor-dependent mitogenesis9,10and neurosecretion11,12; it is redistributed from plasma membrane to cytoplasm when phosphorylated13-15 and is involved in leukocyte motility14,15. Here we report that MARCKS is a filamentous (F) 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 PKC signal transduction pathways in the regulation of the actin cytoskeleton.

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DO - 10.1038/356618a0

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EP - 622

JO - Nature

JF - Nature

IS - 6370

ER -

MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin

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