A Role for CAP, a Novel, Multifunctional Src Homology 3 Domain-containing Protein in Formation of Actin Stress Fibers and Focal Adhesions

Ribon, Vered; Herrera, Román; Kay, Brian K.; Saltiel, Alan R.

doi:10.1074/jbc.273.7.4073

Cited by 102 publications

(95 citation statements)

References 46 publications

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“…Vinexin belongs to a novel protein family, which consists of vinexin, c-Cbl-associated protein (CAP)/ponsin, and Arg-binding protein 2 (ArgBP2) (19,(42)(43)(44). These proteins share one sorbin homology domain in the N-terminal region and three SH3 domains in the C-terminal region.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Signal-regulated Kinase Activated by Epidermal Growth Factor and Cell Adhesion Interacts with and Phosphorylates Vinexin

Mitsushima

Suwa

Amachi

et al. 2004

Journal of Biological Chemistry

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Extracellular signal-regulated kinase 1/2 (ERK1/2) is activated by various extracellular stimuli including growth factors and cytokines and plays a pivotal role in regulating cell proliferation and differentiation by phosphorylating nuclear transcription factors. Recently, it was reported that activated ERK1/2 also concentrates at adhesion sites and regulates cell spreading and migration. Vinexin is a focal adhesion protein regulating both cell spreading and growth factor signaling. We show here that vinexin was directly phosphorylated by ERK1/2 upon stimulation with growth factors. ERK1/2 phosphorylated the linker region of vinexin between the second and third SH3 domains. Site-directed mutagenesis revealed that ERK2 mainly phosphorylated the serine 189 residue of vinexin ␤. Furthermore, vinexin ␤ interacted with ERK1/2 both in vitro and in vivo. Vinexin interacted with the active but not inactive form of ERK1/2. A putative DEF (docking for ERK FXFP) domain located in the linker region of vinexin was required for the interaction with ERK1/2 and efficient phosphorylation of vinexin ␤ by ERK2. Finally, we showed that cell adhesion to fibronectin also induced the association of vinexin ␤ with ERK2 and the phosphorylation of vinexin ␤. Furthermore, vinexin and ERK were co-localized to the periphery of cells during cell spreading on fibronectin. Together, these results suggest that vinexin is a novel substrate of ERK2 and may play roles in ERK-dependent cell regulation during cell spreading as well as in growth factor-induced responses.Mitogen-activated protein kinase (MAPK) 1 consists of four subfamilies, extracellular signal-regulated kinase 1/2 (ERK1/ 2), c-Jun N-terminal kinase/stress-activated kinase, p38MAPK, and ERK5. ERK1/2 is mainly activated by various growth factors and regulates a diverse array of cellular events including cell proliferation, survival, and differentiation (1, 2). Many extracellular signals activate membrane receptors, including receptor tyrosine kinases, G protein-coupled receptors, or integrins, leading to the activation of Raf. Activated Raf, in turn, activates MEK (MAPK/ERK kinase) by the direct phosphorylation of dual serine residues. Activated MEK also directly phosphorylates and activates ERK1/2. Once activated, ERK1/2 enters the nucleus and phosphorylates nuclear transcription factors, including Elk-1, Sap1, c-Myc, and c-Fos (3).Recently, ERK has been shown to play crucial roles in regulating cell adhesion and cell migration independent of its nuclear functions (4 -7). ERK is involved in the migration of breast cancer cells stimulated by urokinase-type tissue plasminogen activator. Neither de novo gene transcription nor protein synthesis is required for this process (5). Activation of ERK is also suggested to be involved in the chemotaxis or the extension of pseudopodia, probably through the phosphorylation of cytoplasmic proteins (8, 9). Furthermore, ERK is well known to be activated by integrin engagement and to be localized to adhesion sites (7, 10 -14). Although some cytoplasm...

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Section: Discussionmentioning

confidence: 99%

Extracellular Signal-regulated Kinase Activated by Epidermal Growth Factor and Cell Adhesion Interacts with and Phosphorylates Vinexin

Mitsushima

Suwa

Amachi

et al. 2004

Journal of Biological Chemistry

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“…Sorbin and SH3 domain-containing 1 (SORBS1) is a human homolog of c-Cbl-associated protein (CAP), 24 which is an important signaling molecule in insulin stimulation of glucose uptake in mouse adipocytes. [24][25][26][27] Phosphorylation of c-Cbl results in the dissociation of the c-Cbl-CAP complex from the insulin receptor and its translocation to a lipid raft domain of the plasma membrane. Subsequent Genetic variants and hypertension Y Yamada et al resistance.…”

Section: Discussionmentioning

confidence: 99%

Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals

Yamada

Ando

Shimokata³

2009

Hypertens Res

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Although various loci and genes have been implicated in predisposition to hypertension by genetic linkage analyses and candidate gene association studies, the genes that confer susceptibility to this condition remain to be identified definitively. We have now examined the relationships of 22 candidate gene polymorphisms with the prevalence of hypertension and with blood pressure (BP) in a 6-year population-based longitudinal cohort study and observed significant relationships of three polymorphisms of SORBS1, GCK and WISP1 with hypertension. The 2233 subjects (1106 women, 1127 men) were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases in Japan. BP was measured with subjects having rested in the sitting position for at least 15 min. Genotypes for the 682A-G (Thr228Ala) polymorphism of SORBS1, the À30G-A polymorphism of GCK and the 2364A-G polymorphism of WISP1 were determined by melting curve analysis. Longitudinal analysis with a generalized estimating equation revealed that the polymorphisms of SORBS1 and GCK and that of WISP1 were significantly associated with the prevalence of hypertension in women and men, respectively. Longitudinal analysis with a mixed-effect model revealed that the polymorphism of SORBS1 was significantly related to diastolic BP in women and that those of GCK and WISP1 were significantly related to both systolic and diastolic BP in women and men, respectively. These results suggest that SORBS1 and GCK are susceptibility loci for hypertension in Japanese women and that WISP1 is such a locus in men.

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“…GIP-11 is PIG3, a quinone oxidoreductase . GIP-12 is Ponsin/SH3/P12/ CAP/FLAF2 (Mandai et al, 1999;Ribon et al, 1998a). GIP-13 is APOBEC-2, a cytosine deaminase mRNA editing protein (Liao et al, 1999).…”

Section: Gip-6mentioning

confidence: 99%

“…It is through these SH3 domains that Ponsin protein interacts with Vinculin, an F-actin binding protein, at cell-cell and cell-matrix adherens junctions or with Afadin at Zonula adherens (Mandai et al, 1999). In the role of an identical protein, CAP, it was demonstrated that the Ponsin/SH3P12/CAP/FLAF2 protein also directly interacts with the non-receptor focal adhesion tyrosine kinase p125 FAK (Ribon et al, 1998a). Expression of Ponsin/SH3P12/CAP/FLAF2 in 3T3 ®broblasts induced formation of stress ®bres and focal adhesions.…”

Section: Gip-12mentioning

confidence: 99%

Isolation and characterization of sixteen novel p53 response genes

Kostic

Shaw

2000

Oncogene

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A Role for CAP, a Novel, Multifunctional Src Homology 3 Domain-containing Protein in Formation of Actin Stress Fibers and Focal Adhesions

Cited by 102 publications

References 46 publications

Extracellular Signal-regulated Kinase Activated by Epidermal Growth Factor and Cell Adhesion Interacts with and Phosphorylates Vinexin

Extracellular Signal-regulated Kinase Activated by Epidermal Growth Factor and Cell Adhesion Interacts with and Phosphorylates Vinexin

Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals

Isolation and characterization of sixteen novel p53 response genes

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