Activation of Rac and tyrosine phosphorylation of cytokine receptors induced by cross-linking of integrin α4β1 and cell adhesion in hematopoietic cells

Kanda, Eiichiro; Jin, Zhen-Hua; Mizuchi, Daisuke; Arai, Ayako; Miura, Osamu

doi:10.1016/s0006-291x(03)00075-5

Cited by 12 publications

(10 citation statements)

References 33 publications

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“…In particular, Cbl recruits Crk and the p85 subunit of PI 3-kinase, which are involved in Rac-dependent lamellipodia formation in the neurite growth cone. lamellipodia and membrane ruffles in different cell types, including neuronal cells (Hall, 1998;Hawkins et al, 1995;Heldin et al, 1998;Kanda et al, 2003;Wennstrom et al, 1994). In our model of neurite growth of PC12 cells, overexpression of tyrosine mutants of Cbl (Cbl-Y700,774F and Cbl-Y700,731,774F), treatment with the PI 3-kinase inhibitor LY294002 or overexpression of dominant negative forms of CrkII (Fig.…”

Section: Discussionmentioning

confidence: 99%

Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites

Haglund

Ivanković-Dikić

Shimokawa

et al. 2004

Journal of Cell Science

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Protein tyrosine kinase Pyk2 and multifunctional adaptor protein Cbl are implicated in the regulation of the cytoskeleton in several cell types. We report that Pyk2 and Cbl form a signaling complex that is translocated to lipid rafts and is enriched in growth cones of differentiating PC12 cells following growth factor stimulation. We found that Pyk2 and Cbl interacted with the adaptor protein ArgBP2, which also bound to flotillin-1, a component of lipid raft microdomains. These interactions contributed to recruitment of the Pyk2/Cbl complex to lipid raft compartments. In addition, Pyk2, Cbl and ArgBP2 were found co-localized with actin in axons and growth cones of differentiated PC12 cells. Moreover, co-expression of Pyk2, ArgBP2 and Cbl facilitated growth factor-induced formation of lamellipodia at the tip of neurites. Formation of these growth cone lamellipodia was dependent on intact lipid rafts and the Cbl-associated effectors Crk and phosphatidylinositol 3 (PI 3)-kinase. Our results indicate that recruitment of Pyk2/Cbl complexes to lipid rafts participates in growth factor-induced regulation of the actin cytoskeleton in growing neurites.

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Section: Discussionmentioning

confidence: 99%

Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites

Haglund

Ivanković-Dikić

Shimokawa

et al. 2004

Journal of Cell Science

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“…To this end, it remains unclear how ␣4-associated signaling promotes Rac activation at the leading edge of migrating cells (15). Although ␣4␤1 activation can promote the tyrosine phosphorylation of a broad range of proteins (14) including Pyk2 and FAK (6,19,41), it is unclear whether differences in ␣4␤1-and ␣5␤1-stimulated cell motility reflect a novel ␣4 cytoplasmic domain linkage to PTK activation as opposed to enhanced ␤1-mediated signaling.…”

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confidence: 99%

Integrin α4β1 Promotes Focal Adhesion Kinase-Independent Cell Motility via α4 Cytoplasmic Domain-Specific Activation of c-Src

Hsia

Lim

Bernard‐Trifilo

et al. 2005

Molecular and Cellular Biology

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The fibronectin binding integrins ␣5␤1 and ␣4␤1 generate signals pivotal for cell migration through distinct yet undefined mechanisms. For ␣5␤1, ␤1-mediated activation of focal adhesion kinase (FAK) promotes c-Src recruitment to FAK and the formation of a FAK-Src signaling complex. Herein, we show that FAK expression is essential for ␣5␤1-stimulated cell motility and that exogenous expression of human ␣4 in FAK-null fibroblasts forms a functional ␣4␤1 receptor that promotes robust cell motility equal to the ␣5␤1 stimulation of wild-type and FAK-reconstituted fibroblasts. ␣4␤1-stimulated FAK-null cell spreading and motility were dependent on the integrity of the ␣4 cytoplasmic domain, independent of direct paxillin binding to ␣4, and were not affected by PRNK expression, a dominant-negative inhibitor of Pyk2. ␣4 cytoplasmic domain-initiated signaling led to a ϳ4-fold activation of c-Src which did not require paxillin binding to ␣4. Notably, ␣4-stimulated cell motility was inhibited by catalytically inactive receptor protein-tyrosine phosphatase ␣ overexpression and blocked by the p50Csk phosphorylation of c-Src at Tyr-529. ␣4␤1-stimulated cell motility of triple-null Src ؊/؊ , c-Yes ؊/؊ , and Fyn ؊/؊ fibroblasts was dependent on c-Src reexpression that resulted in p130Cas tyrosine phosphorylation and Rac GTPase loading. As p130Cas phosphorylation and Rac activation are common downstream targets for ␣5␤1-stimulated FAK activation, our results support the existence of a novel ␣4 cytoplasmic domain connection leading to c-Src activation which functions as a FAK-independent linkage to a common motility-promoting signaling pathway.Integrins are a family of heterodimeric ␣/␤ transmembrane cell adhesion receptors that play important roles in the regulation of cell migration during development, wound healing, inflammation, and the spread of tumor cells. Integrins do not possess intrinsic catalytic activity, and thus, signaling events are mediated by either lateral association with other receptors (8,52) or the clustering of signaling proteins with integrin cytoplasmic domains (44). As the composition of integrin signaling complexes is diverse and remains poorly defined (16), it is important to identify the molecular signaling signature of integrins that share a common ␤ subunit, bind to a common substrate such as fibronectin (FN), and function to promote cell motility. The FN binding integrins ␣5␤1 and ␣4␤1 share these properties.␣5␤1 is considered to be the classical FN receptor, with binding occurring within FN repeats III-9 and III-10 (33, 37). Rapid activation of protein-tyrosine kinases (PTKs) is one of the first signaling events associated with ␣5␤1 binding to FN, and signals generated by the ␤1 cytoplasmic domain are important in promoting cell motility (12, 39). Focal adhesion kinase (FAK) is recruited to sites of ␣5␤1 clustering through FAK C-terminal domain interactions with ␤1-integrin binding proteins such as talin and adaptor proteins such as paxillin (34). FN-stimulated FAK activation results in increased F...

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“…Human erythropoietin is an important inducer of erythropoiesis . Upon Epo stimulation, CrkL is recruited to EpoR in the EpoR cytoplasmic domain and activates the downstream signalling pathways leading to erythroid differentiation . Our results showed that overexpression of CRKL increased the erythroid differentiation of K562 cells, while silencing of CRKL by siRNA significantly attenuated hemin‐induced erythroid differentiation of K562 cells.…”

Section: Discussionmentioning

confidence: 62%

Quantitative proteomics reveals that miR‐222 inhibits erythroid differentiation by targeting BLVRA and CRKL

Jiang

Wang

et al. 2018

Cell Biochemistry & Function

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miR-222 plays an important role in erythroid differentiation, but the potential targets of miR-222 in the regulation of erythroid differentiation remain to be determined. The target genes of miR-222 were identified by proteomics combined with bioinformatics analysis in this study. Thirteen proteins were upregulated, and 13 were downregulated in K562 cells following transfection with miR-222 inhibitor for 24 and 48 hours. Among these proteins, BLVRA and CRKL were upregulated after transfection of miR-222 inhibitor in K562 cells and human CD34+ HPCs. Moreover, miR-222 mimics reduced and miR-222 inhibitor enhanced the mRNA and protein levels of both BLVRA and CRKL. Luciferase assay showed that miR-222 directly targeted 3'-UTR of BLVRA and CRKL. In addition, overexpression of either BLVRA or CRKL or both increased the erythroid differentiation of K562 cells, while silencing of either BLVRA or CRKL or both by siRNA significantly attenuated hemin-induced erythroid differentiation of K562 cells. Our results indicated that BLVRA and CRKL are targets of miR-222.

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Activation of Rac and tyrosine phosphorylation of cytokine receptors induced by cross-linking of integrin α4β1 and cell adhesion in hematopoietic cells

Cited by 12 publications

References 33 publications

Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites

Recruitment of Pyk2 and Cbl to lipid rafts mediates signals important for actin reorganization in growing neurites

Integrin α4β1 Promotes Focal Adhesion Kinase-Independent Cell Motility via α4 Cytoplasmic Domain-Specific Activation of c-Src

Quantitative proteomics reveals that miR‐222 inhibits erythroid differentiation by targeting BLVRA and CRKL

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