Parvin: Difference between revisions

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[[Image:Alpha_parvin.png|thumb|434px|right|Alpha-parvin domain composition and regions involved in the interactions with the binding partners]]

===Alpha-parvin phosphorylation and cell migration===

Alpha-parvin possesses 6 putative proline-directed serine/threonine phosphorylation targets (residues 4, 8, 14, 16, 19, 61), of which serines 4 and 8 were shown to be the most important. Phosphorylation of alpha-parvin at serines 4 and 8 is correlated with the tightly regulated process of FA turnover during cell migration. Firstly, phosphorylation of these residues by cyclin B1/cdc2 is observed in the context of mitosis, whereby it contributes to FA disassembly required for cell-rounding prior to cell division, suggesting it may cause a similar effect during cell migration.<ref>PMID: 11931650</ref> Indeed, in migrating cells these residues are observed to be phosphorylated<ref>PMID: 15353548</ref>, likely as a result of MAP kinase<ref>PMID: 14636584</ref> and/or PI3K<ref>PMID: 12960424</ref>. Secondly, phosphomimetic mutations of serines 4 and 8 to aspartates result in faster migration and spreading, while mutations preventing phosphorylation impair these processes.<ref>PMID: 15353548</ref> Finally, as has already been mentioned in the introduction, knock-out mice phenotype (embryonic lethality due to severe cardiovascular defects) suggests alpha-parvin deficiency results in impaired directional migration of endothelial cells during embryonic development, heart development in particular.<ref>PMID: 19798050</ref> The macroscopic effects of alpha-parvin phosphorylation likely result from the altered affinity for its binding partners. So far it has been demonstrated that phosphorylation at serines 4 and 8 affects binding of alpha-parvin to TESK1 and CdGAP. When TESK1 is bound to alpha-parvin it is prevented from severing actin fibres. TESK1 is thought to be released from inhibition upon alpha-parvin phosphorylation and this can contribute to the decomposition of actin fibres and FA disassembly.<ref>PMID: 15817463</ref> CdGAP, on the other hand, is involved in the regulation of small GTPase signalling, which accounts for changes in cytoskeletal contractability during cell migration.<ref>PMID: 16860736</ref> Evidence suggesting that also the interaction with ILK is affected by phosphorylation is not strong<ref>PMID: 15872073</ref><ref>PMID: 12960424</ref>, but it is likely that this or yet other binding partners bind in the phosphorylation-dependent manner.

Alpha-parvin possesses 6 putative proline-directed serine/threonine phosphorylation targets (residues 4, 8, 14, 16, 19, 61), of which serines 4 and 8 were shown to be the most important. Phosphorylation of alpha-parvin at serines 4 and 8 is correlated with the tightly regulated process of FA turnover during cell migration. Firstly, phosphorylation of these residues by cyclin B1/cdc2 is observed in the context of mitosis, whereby it contributes to FA disassembly required for cell-rounding prior to cell division, suggesting it may cause a similar effect during cell migration.<ref>PMID: 11931650</ref> Indeed, in migrating cells these residues are observed to be phosphorylated<ref>PMID: 15353548</ref>, likely as a result of MAP kinase<ref>PMID: 14636584</ref> and/or [[PI3K]]<ref>PMID: 12960424</ref>. Secondly, phosphomimetic mutations of serines 4 and 8 to aspartates result in faster migration and spreading, while mutations preventing phosphorylation impair these processes.<ref>PMID: 15353548</ref> Finally, as has already been mentioned in the introduction, knock-out mice phenotype (embryonic lethality due to severe cardiovascular defects) suggests alpha-parvin deficiency results in impaired directional migration of endothelial cells during embryonic development, heart development in particular.<ref>PMID: 19798050</ref> The macroscopic effects of alpha-parvin phosphorylation likely result from the altered affinity for its binding partners. So far it has been demonstrated that phosphorylation at serines 4 and 8 affects binding of alpha-parvin to TESK1 and CdGAP. When TESK1 is bound to alpha-parvin it is prevented from severing actin fibres. TESK1 is thought to be released from inhibition upon alpha-parvin phosphorylation and this can contribute to the decomposition of actin fibres and FA disassembly.<ref>PMID: 15817463</ref> CdGAP, on the other hand, is involved in the regulation of small GTPase signalling, which accounts for changes in cytoskeletal contractability during cell migration.<ref>PMID: 16860736</ref> Evidence suggesting that also the interaction with ILK is affected by phosphorylation is not strong<ref>PMID: 15872073</ref><ref>PMID: 12960424</ref>, but it is likely that this or yet other binding partners bind in the phosphorylation-dependent manner.

==Structure and function==

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@@ Line 12: / Line 12: @@
 [[Image:Alpha_parvin.png|thumb|434px|right|Alpha-parvin domain composition and regions involved in the interactions with the binding partners]]
 ===Alpha-parvin phosphorylation and cell migration===
-Alpha-parvin possesses 6 putative proline-directed serine/threonine phosphorylation targets (residues 4, 8, 14, 16, 19, 61), of which serines 4 and 8 were shown to be the most important. Phosphorylation of alpha-parvin at serines 4 and 8 is correlated with the tightly regulated process of FA turnover during cell migration. Firstly, phosphorylation of these residues by cyclin B1/cdc2 is observed in the context of mitosis, whereby it contributes to FA disassembly required for cell-rounding prior to cell division, suggesting it may cause a similar effect during cell migration.<ref>PMID: 11931650</ref> Indeed, in migrating cells these residues are observed to be phosphorylated<ref>PMID: 15353548</ref>, likely as a result of MAP kinase<ref>PMID: 14636584</ref> and/or PI3K<ref>PMID: 12960424</ref>. Secondly, phosphomimetic mutations of serines 4 and 8 to aspartates result in faster migration and spreading, while mutations preventing phosphorylation impair these processes.<ref>PMID: 15353548</ref> Finally, as has already been mentioned in the introduction, knock-out mice phenotype (embryonic lethality due to severe cardiovascular defects) suggests alpha-parvin deficiency results in impaired directional migration of endothelial cells during embryonic development, heart development in particular.<ref>PMID: 19798050</ref> The macroscopic effects of alpha-parvin phosphorylation likely result from the altered affinity for its binding partners. So far it has been demonstrated that phosphorylation at serines 4 and 8 affects binding of alpha-parvin to TESK1 and CdGAP. When TESK1 is bound to alpha-parvin it is prevented from severing actin fibres. TESK1 is thought to be released from inhibition upon alpha-parvin phosphorylation and this can contribute to the decomposition of actin fibres and FA disassembly.<ref>PMID: 15817463</ref> CdGAP, on the other hand, is involved in the regulation of small GTPase signalling, which accounts for changes in cytoskeletal contractability during cell migration.<ref>PMID: 16860736</ref> Evidence suggesting that also the interaction with ILK is affected by phosphorylation is not strong<ref>PMID: 15872073</ref><ref>PMID: 12960424</ref>, but it is likely that this or yet other binding partners bind in the phosphorylation-dependent manner.
+Alpha-parvin possesses 6 putative proline-directed serine/threonine phosphorylation targets (residues 4, 8, 14, 16, 19, 61), of which serines 4 and 8 were shown to be the most important. Phosphorylation of alpha-parvin at serines 4 and 8 is correlated with the tightly regulated process of FA turnover during cell migration. Firstly, phosphorylation of these residues by cyclin B1/cdc2 is observed in the context of mitosis, whereby it contributes to FA disassembly required for cell-rounding prior to cell division, suggesting it may cause a similar effect during cell migration.<ref>PMID: 11931650</ref> Indeed, in migrating cells these residues are observed to be phosphorylated<ref>PMID: 15353548</ref>, likely as a result of MAP kinase<ref>PMID: 14636584</ref> and/or [[PI3K]]<ref>PMID: 12960424</ref>. Secondly, phosphomimetic mutations of serines 4 and 8 to aspartates result in faster migration and spreading, while mutations preventing phosphorylation impair these processes.<ref>PMID: 15353548</ref> Finally, as has already been mentioned in the introduction, knock-out mice phenotype (embryonic lethality due to severe cardiovascular defects) suggests alpha-parvin deficiency results in impaired directional migration of endothelial cells during embryonic development, heart development in particular.<ref>PMID: 19798050</ref> The macroscopic effects of alpha-parvin phosphorylation likely result from the altered affinity for its binding partners. So far it has been demonstrated that phosphorylation at serines 4 and 8 affects binding of alpha-parvin to TESK1 and CdGAP. When TESK1 is bound to alpha-parvin it is prevented from severing actin fibres. TESK1 is thought to be released from inhibition upon alpha-parvin phosphorylation and this can contribute to the decomposition of actin fibres and FA disassembly.<ref>PMID: 15817463</ref> CdGAP, on the other hand, is involved in the regulation of small GTPase signalling, which accounts for changes in cytoskeletal contractability during cell migration.<ref>PMID: 16860736</ref> Evidence suggesting that also the interaction with ILK is affected by phosphorylation is not strong<ref>PMID: 15872073</ref><ref>PMID: 12960424</ref>, but it is likely that this or yet other binding partners bind in the phosphorylation-dependent manner.
 ==Structure and function==