PMID:23118220

Citation	Gawecka, JE, Young-Robbins, SS, Sulzmaier, FJ, Caliva, MJ, Heikkilä, MM, Matter, ML and Ramos, JW (2012) RSK2 protein suppresses integrin activation and fibronectin matrix assembly and promotes cell migration. J. Biol. Chem. 287:43424-37
Abstract	Modulation of integrin activation is important in many cellular functions including adhesion, migration, and assembly of the extracellular matrix. RSK2 functions downstream of Ras/Raf and promotes tumor cell motility and metastasis. We therefore investigated whether RSK2 affects integrin function. We report that RSK2 mediates Ras/Raf inactivation of integrins. As a result, we find that RSK2 impairs cell adhesion and integrin-mediated matrix assembly and promotes cell motility. Active RSK2 appears to affect integrins by reducing actin stress fibers and disrupting focal adhesions. Moreover, RSK2 co-localizes with the integrin activator talin and is present at integrin cytoplasmic tails. It is thereby in a position to modulate integrin activation and integrin-mediated migration. Activation of RSK2 promotes filamin phosphorylation and binding to integrins. We also find that RSK2 is activated in response to integrin ligation to fibronectin. Thus, RSK2 could participate in a feedback loop controlling integrin function. These results reveal RSK2 as a key regulator of integrin activity and provide a novel mechanism by which it may promote cell migration and cancer metastasis.
Links	PubMed PMC3527930 Online version:10.1074/jbc.M112.423046
Keywords	Animals; CHO Cells; Cell Adhesion/physiology; Cell Movement/physiology; Contractile Proteins/genetics; Contractile Proteins/metabolism; Cricetinae; Cricetulus; Enzyme Activation/physiology; HeLa Cells; Humans; Integrins/genetics; Integrins/metabolism; Microfilament Proteins/genetics; Microfilament Proteins/metabolism; Neoplasm Metastasis; Neoplasms/genetics; Neoplasms/metabolism; Neoplasms/pathology; Phosphorylation/physiology; Ribosomal Protein S6 Kinases, 90-kDa/genetics; Ribosomal Protein S6 Kinases, 90-kDa/metabolism; Talin/genetics; Talin/metabolism; raf Kinases/genetics; raf Kinases/metabolism; ras Proteins/genetics; ras Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:MK01		GO:0033624: negative regulation of integrin activation	ECO:0000314:		P		Figure 1 - RSK2 inhibits integrin activation	complete CACAO 7413
HUMAN:MK01		GO:0007162: negative regulation of cell adhesion	ECO:0000314:		P		Figure 1 - RSK2 inhibits integrin activation and impairs cell adhesion.	complete CACAO 7416
HUMAN:MK01		GO:0033629: negative regulation of cell adhesion mediated by integrin	ECO:0000314:		P		Figure 2 - RSK2 inhibits integrin activation and impairs cell adhesion	complete CACAO 7419
HUMAN:MK01		GO:1901202: negative regulation of extracellular matrix assembly	ECO:0000314:		P		Figure 2-RSK2 inhibits fibronectin matrix assembly	complete CACAO 7420

References

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