Phosphorylation of Hic‐5 at tyrosine 60 by CAKβ and Fyn

Ishino, Masaho; Aoto, Hiroshi; Sasaski, Hiroko; Suzuki, Rumiko; Sasaki, Terukatsu

doi:10.1016/s0014-5793(00)01597-0

Cited by 35 publications

(45 citation statements)

References 37 publications

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“…Inhibition of p38 MAPK had no effect on NE-induced Hic-5 activation (Table 1). This strongly suggests that NE induces Hic-5 tyrosine phosphorylation through PYK2, in agreement with studies in cells (23), and that Src kinases are upstream activators of this pathway. Additionally, the stimulation of RMSAs by NE causes Hic-5 to move from the membrane fraction to the cytosol (Fig.…”

Section: Resultssupporting

confidence: 88%

“…However, it is phosphorylated by PYK2, a calcium-dependent homologue of p125FAK (16,51), suggesting different cellular functions for the two proteins. Hic-5 was shown to be a substrate for PYK2 (23), and in COS cells and rat fibroblasts, it was shown to interact with PYK2 (31), whereas in rat kidney epithelial cells (24), Hic-5 was shown to associate with Hsp27. Hic-5 has been identified in smooth muscle tissues (58), and PYK2, also present in smooth muscle, is activated by ANG II (7,59) and norepinephrine (NE) (38), causing its translocation from cytosol to the cytoskeleton.…”

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confidence: 99%

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Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries

Srinivasan¹,

Forman²,

Quinlan³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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regulation of small artery contractility by vasoconstrictors is important for vascular function, and actin cytoskeleton remodeling is required for contraction. p38 MAPK and tyrosine kinases are implicated in actin polymerization and contraction through heat shock protein 27 (Hsp27) and the cytoskeletal protein paxillin, respectively. We evaluated the roles of downstream targets of p38 MAPK and tyrosine kinases in cytoskeletal reorganization and contraction and whether the two signaling pathways regulate contraction independent of each other. We identified the expression of the paxillin homologue hydrogen peroxide-inducible clone-5 (Hic-5) and showed its activation by norepinephrine (NE) in a Src-dependent manner. Furthermore, we demonstrated a NE-induced interaction of proline-rich tyrosine kinase-2 (PYK2) but not Src or p125 focal adhesion kinase with Hic-5. This interaction was Src dependent, suggesting that Hic-5 was a substrate for PYK2 downstream from Src. The activation of Hic-5 induced its relocalization to the cytosol. The parallel activation of Hsp27 by NE was p38 MAPK dependent and led to its dissociation from actin filaments and translocation from membrane to cytosol and increased actin polymerization. Both Hsp27 and Hic-5 activation resulted in their association within the same time frame as NEinduced contraction, and the inhibition of either p38 MAPK or Src inhibited the interaction between Hsp27 and Hic-5 and the contractile response. Furthermore, combined p38 MAPK and Src inhibition had no greater effect on contraction than individual inhibition, suggesting that the two pathways act through a common mechanism. These data show that NE-induced activation and the association of Hsp27 and Hic-5 are required for the reorganization of the actin cytoskeleton and force development in small arteries.

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Section: Resultssupporting

confidence: 88%

mentioning

confidence: 99%

Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries

Srinivasan¹,

Forman²,

Quinlan³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…A paxillin mutant that is unable to bind FAK exhibits reduced steady state levels of phosphotyrosine, reduced tyrosine phosphorylation following cell adhesion to ®bronectin and reduced tyrosine phosphorylation in Src transformed cells (Thomas et al, 1999b). CAKb can induce tyrosine phosphorylation of hic-5 and the induction of tyrosine phosphorylation depends upon the binding of hic-5 to the C-terminus of CAKb (Ishino et al, 2000b). These data support the contention that association of paxillin with FAK and CAKb is a mechanism to promote tyrosine phosphorylation of paxillin.…”

Section: Kinasesmentioning

confidence: 99%

“…Thus functions speci®c to each protein might be mediated by these unique sequences. Although hic-5 does not contain the Crkbinding sites in its N-terminus, tyrosine 60 is a site of phosphorylation and serves as a binding site for Csk (Ishino et al, 2000b). Recruitment of Csk could lead to further tyrosine phosphorylation of paxillin or to phosphorylation of Src family kinases to inhibit their catalytic activity.…”

Section: Consequences Of Tyrosine Phosphorylation Of Paxillinmentioning

confidence: 99%

Paxillin: a focal adhesion-associated adaptor protein

2001

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Paxillin is a focal adhesion-associated, phosphotyrosinecontaining protein that may play a role in several signaling pathways. Paxillin contains a number of motifs that mediate protein ± protein interactions, including LD motifs, LIM domains, an SH3 domain-binding site and SH2 domain-binding sites. These motifs serve as docking sites for cytoskeletal proteins, tyrosine kinases, serine/ threonine kinases, GTPase activating proteins and other adaptor proteins that recruit additional enzymes into complex with paxillin. Thus paxillin itself serves as a docking protein to recruit signaling molecules to a speci®c cellular compartment, the focal adhesions, and/ or to recruit speci®c combinations of signaling molecules into a complex to coordinate downstream signaling. The biological function of paxillin coordinated signaling is likely to regulate cell spreading and motility. Oncogene (2001) 20, 6459 ± 6472.

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“…paxillin was shown to bind Src either directly or via Pyk2 (31), Hic-5 can bind Fyn (42), and LPXN can interact with Src in osteoclasts (34). Because we demonstrated that LPXN was tyrosine-phosphorylated upon BCR cross-linking and it is known that Lyn is the predominant Src family tyrosine kinase found in B cells (43), we investigated whether LPXN can physically interact with Lyn.…”

Section: Leupaxin Is Activated Upon Bcr Engagement In Humanmentioning

confidence: 99%

Leupaxin Negatively Regulates B Cell Receptor Signaling

Chew

Lam

2007

Journal of Biological Chemistry

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The role of the paxillin superfamily of adaptor proteins in B cell antigen receptor (BCR) signaling has not been studied previously. We show here that leupaxin (LPXN), a member of this family, was tyrosine-phosphorylated and recruited to the plasma membrane of human BJAB lymphoma cells upon BCR stimulation and that it interacted with Lyn (a critical Src family tyrosine kinase in BCR signaling) in a BCR-induced manner. LPXN contains four leucine-rich sequences termed LD motifs, and serial truncation and specific domain deletion of LPXN indicated that its LD3 domain is involved in the binding of Lyn.

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Phosphorylation of Hic‐5 at tyrosine 60 by CAKβ and Fyn

Cited by 35 publications

References 37 publications

Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries

Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries

Paxillin: a focal adhesion-associated adaptor protein

Leupaxin Negatively Regulates B Cell Receptor Signaling

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