Protein kinase A activity is regulated by actomyosin contractility during cell migration and is required for durotaxis

McKenzie, Andrew J.; Svec, Kathryn V.; Williams, Tamara F.; Howe, Alan K.

doi:10.1091/mbc.e19-03-0131

Cited by 22 publications

(35 citation statements)

References 118 publications

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“…Once activated, PKA phosphorylates its substrates, such as CREB, Raf, Bad and GSK3 [ 25 – 27 ], and then regulates gene expression, cell survival and migration. Recent study indicates that PKA is an actomyosin contractility-regulated effector of cellular mechanotransduction and a regulator of mechanically guided cell migration [ 28 ]. PKA also phosphorylates CDC42 interacting protein 4 (CIP4), a coordinator of membrane deformation and actin polymerization, and promotes cancer cell invasion and metastasis [ 29 ].…”

Section: The Molecular Targets and Roles Of Camp In Cancer Cell Growtmentioning

confidence: 99%

Complex roles of cAMP–PKA–CREB signaling in cancer

et al. 2020

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Cyclic adenosine monophosphate (cAMP) is the first discovered second messenger, which plays pivotal roles in cell signaling, and regulates many physiological and pathological processes. cAMP can regulate the transcription of various target genes, mainly through protein kinase A (PKA) and its downstream effectors such as cAMP-responsive element binding protein (CREB). In addition, PKA can phosphorylate many kinases such as Raf, GSK3 and FAK. Aberrant cAMP–PKA signaling is involved in various types of human tumors. Especially, cAMP signaling may have both tumor-suppressive and tumor-promoting roles depending on the tumor types and context. cAMP–PKA signaling can regulate cancer cell growth, migration, invasion and metabolism. This review highlights the important roles of cAMP–PKA–CREB signaling in tumorigenesis. The potential strategies to target this pathway for cancer therapy are also discussed.

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Section: The Molecular Targets and Roles Of Camp In Cancer Cell Growtmentioning

confidence: 99%

Complex roles of cAMP–PKA–CREB signaling in cancer

et al. 2020

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“…One interesting possibility would be that cell deformation by itself, i.e., membrane stretching, could be the driving force of cAMP bursts. Indeed, the increase in membrane tension generated during migration (Pontes et al, 2017), might drive a cAMP increase, as suggested in other systems (Alenghat et al, 2009;McKenzie et al, 2020). In this context, the cAMPinduced recruitment of actomyosin would reduce this stretch by retracting the lamellipodium, and therefore inhibit the synthesis of cAMP.…”

Section: Discussionmentioning

confidence: 89%

“…Interestingly, in other cell types, cAMP seems to play a more complex role in cell migration through its compartmentalization. In fibroblasts or epithelial cells, an increase of cAMP-activated protein kinase (PKA) activity at the leading edge has been reported to promote cell migration ( Howe et al, 2005 ; Lim et al, 2008 ; McKenzie et al, 2020 ). Conversely, in neutrophils, local increases in cAMP promote uropod retraction through the regulation of the non-muscle myosin II by PKA ( Liu et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

cAMP Bursts Control T Cell Directionality by Actomyosin Cytoskeleton Remodeling

Simao

Régnier

Taheraly

et al. 2021

Front. Cell Dev. Biol.

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T lymphocyte migration is an essential step to mounting an efficient immune response. The rapid and random motility of these cells which favors their sentinel role is conditioned by chemokines as well as by the physical environment. Morphological changes, underlaid by dynamic actin cytoskeleton remodeling, are observed throughout migration but especially when the cell modifies its trajectory. However, the signaling cascade regulating the directional changes remains largely unknown. Using dynamic cell imaging, we investigated in this paper the signaling pathways involved in T cell directionality. We monitored cyclic adenosine 3′-5′ monosphosphate (cAMP) variation concomitantly with actomyosin distribution upon T lymphocyte migration and highlighted the fact that spontaneous bursts in cAMP starting from the leading edge, are sufficient to promote actomyosin redistribution triggering trajectory modification. Although cAMP is commonly considered as an immunosuppressive factor, our results suggest that, when transient, it rather favors the exploratory behavior of T cells.

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“…membrane stretching, could be the driving force of cAMP bursts. Indeed, the increase in membrane tension generated during migration (23), might drive a cAMP increase, as suggested in other systems (14,24). In this context, the cAMP- cAMP is generally considered as a messenger which dampens immune response (28).…”

Section: Control Of Stable Actin Relocalization By Campmentioning

confidence: 97%

“…Interestingly, in other cell types, cAMP seems to play a more complex role in cell migration through its compartmentalization. Indeed, in fibroblasts or epithelial cells, an increase of cAMP-activated protein kinase (PKA) at the leading edge has been reported to promote cell migration (12)(13)(14). The development of powerful biosensors makes it possible to measure cAMP (15) at the subcellular level even in small cells such as lymphocytes and with a good temporal resolution, and therefore to revisit the role of cAMP in T cell migration.…”

Section: Introductionmentioning

confidence: 99%

cAMP bursts control T cell directionality by actin cytoskeleton remodeling

Simao

Régnier

Taheraly

et al. 2020

Preprint

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AbstractT lymphocyte migration is an essential step to mounting an efficient immune response. The rapid and random motility of these cells which favors their sentinel role is conditioned by chemokines as well as by the physical environment. Morphological changes, underlaid by dynamic actin cytoskeleton remodeling, are observed throughout migration but especially when the cell modifies its trajectory. Using dynamic cell imaging, we investigated the signaling pathways involved in T cell directionality control. We monitored cAMP variation concomitantly with actin distribution upon T lymphocyte migration and highlighted the fact that spontaneous bursts in cAMP starting from the leading edge, are sufficient to promote stable actin redistribution triggering trajectory modification.

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Protein kinase A activity is regulated by actomyosin contractility during cell migration and is required for durotaxis

Cited by 22 publications

References 118 publications

Complex roles of cAMP–PKA–CREB signaling in cancer

Complex roles of cAMP–PKA–CREB signaling in cancer

cAMP Bursts Control T Cell Directionality by Actomyosin Cytoskeleton Remodeling

cAMP bursts control T cell directionality by actin cytoskeleton remodeling

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