Interaction of two proline-rich sequences of cell adhesion kinase β with SH3 domains of p130Cas-related proteins and a GTPase-activating protein, Graf

Ohba, Takeaki; Ishino, Masaho; Aoto, Hiroshi; Sasaki, Terukatsu

doi:10.1042/bj3301249

Cited by 66 publications

(42 citation statements)

References 45 publications

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“…During brain development, FAK was shown to interact with both SH2 domains of RasGAP (Serpente et al, 1996). Recently Graf, an SH3 domain-containing GAP molecule for Rho and CDC42, was isolated and shown to associate with FAK as well as with RAFTK/CAK-b via its SH3 domain (Hildebrand et al, 1996;Ohba et al, 1998;Taylor et al, 1998). Thus, our data indicate that the RAFTK-mediated association between GAP molecules and focal adhesion molecules may be a site of convergence for growth factor signaling and Rhomediated cytoskeletal changes.…”

Section: Discussionmentioning

confidence: 55%

RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion

Zrihan-Licht

Settleman

et al. 2000

Oncogene

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Focal adhesions and actin cytoskeleton are involved in cell growth, shape and movement and in tumor invasion. Mitogen-induced changes in actin cytoskeleton are accompanied by changes in the tyrosine phosphorylation of several focal adhesion proteins. In this study, we have investigated the role of RAFTK, a cytoplasmic tyrosine kinase related to focal adhesion kinase (FAK), in heregulin-mediated signal transduction in breast cancer cells. Stimulation of T47D cells with heregulin (HRG) induced the tyrosine phosphorylation of RAFTK and the formation of a multiprotein complex. Analyses of the members of the HRG-stimulated complex revealed that RAFTK is associated with p190 RhoGAP (p190), RasGAP and ErbB-2, and plays an essential role in mediating the tyrosine phosphorylation of p190 by Src. Mutation of the Src binding site within RAFTK (402) abolished the phosphorylation of p190. In addition, upon HRG stimulation of T47D cells, association of ErbB-2 with RAFTK was observed and found to be indirect and mediated by Src. Expression of wild-type RAFTK (WT) signi®cantly increased MDA-MB-435 and MCF-7 breast cancer cell invasion, while expression of the kinasemutated RAFTK-R457 (KM) or the Src binding site mutant RAFTK (402) did not a ect this cell invasion. Furthermore, HRG leads to the activation of MAP kinase which is mediated by RAFTK. These ®ndings indicate that RAFTK serves as a mediator and an integration point between the GAP proteins and HRG-mediated signaling in breast cancer cells, and implicate RAFTK involvement in the MAP kinase pathway and in breast cancer cell invasion.

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Section: Discussionmentioning

confidence: 55%

RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion

Zrihan-Licht

Settleman

et al. 2000

Oncogene

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“…47 In support of this possibility, expression of the Pyk2[H]-interacting proteins Graf, p130 Cas , and Hck are each altered in BCR/ABL þ vs BCR/ABL À Mo7e cells (data not shown), suggesting that modification of Pyk2 [H] signaling may, in fact, occur because effecter molecules (eg Graf) differentially associate with the two PYK2 isoforms. 48 Further studies regarding the effects of Pyk2[H] signaling via its effecter molecules in NL and BCR/ABL þ cells are needed to ascertain whether such a hypothesis might be correct.…”

Section: Discussionmentioning

confidence: 99%

p210BCR/ABL-induced alteration of pre-mRNA splicing in primary human CD34+ hematopoietic progenitor cells

2004

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Chronic myelogenous leukemia (CML) is a malignancy of the human hematopoietic stem cell (HSC) caused by the p210 BCR/ABL oncoprotein. Although alternative splicing of pre-mRNA is a critical determinant of a cell's protein repertoire, it has not been associated with CML pathogenesis. We identified a BCR/ABL-dependent increase in expression of multiple genes involved in pre-mRNA splicing (eg SRPK1, RNA Helicase II/Gu, and hnRNPA2/B1) by subtractive hybridization of cDNA from p210 BCR/ABL -eGFP vs eGFP-transduced umbilical cord blood CD34 þ cells. b1-integrin signaling is important to HSC maintenance and proliferation/differentiation, and is abnormal in CML. As an example of how changes in premRNA processing might contribute to CML pathogenesis, we observed alternative splicing of a gene for a b1-integrinresponsive nonreceptor tyrosine kinase (PYK2), resulting in increased expression of full-length Pyk2 in BCR/ABL-containing cells. Treatment of p210 BCR/ABL -positive cells with the Ablspecific tyrosine kinase inhibitor STI571 reverted PYK2 splicing to a configuration more consistent with normal cells, and correlated with decreased expression of BCR/ABL-induced proteins involved in pre-mRNA processing. Whether altered PYK2 splicing contributes to CML pathogenesis remains undetermined; however, we propose that generic changes in pre-mRNA splicing as a result of p210 BCR/ABL kinase activity may contribute to CML pathogenesis.

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“…In addition to its SH2 domain, it has multiple proline-rich motifs, a PH domain, and multiple potential serine, threonine, and tyrosine phosphorylation sites. PH domains and proline-rich motifs are present in many signaling molecules and are thought to target these proteins to the plasma membrane by binding to phospholipids (50 -52) and constitutively associate with SH3 or WW domain-containing proteins, respectively (53)(54)(55)(56)(57)(58)(59). Therefore, we think it likely that its PH domain targets SH2-B to the plasma membrane, and its proline-rich motifs interact constitutively with signaling molecules containing SH3 domains.…”

Section: Figmentioning

confidence: 99%

SH2-B, a Membrane-associated Adapter, Is Phosphorylated on Multiple Serines/Threonines in Response to Nerve Growth Factor by Kinases within the MEK/ERK Cascade

Rui

Herrington

Carter‐Su

1999

Journal of Biological Chemistry

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SH2-B has been shown to be required for nerve growth factor (NGF)-mediated neuronal differentiation and survival, associate with NGF receptor TrkA, and be tyrosylphosphorylated in response to NGF. In this work, we examined whether NGF stimulates phosphorylation of SH2-B on serines/threonines. NGF promotes a dramatic upward shift in mobility of SH2-B, resulting in multiple forms that cannot be attributed to tyrosyl phosphorylation. Treatment of SH2-B with protein phosphatase 2A, a serine/threonine phosphatase, reduces the many forms to two. PD98059, a MEK inhibitor, dramatically inhibits NGF-promoted phosphorylation of SH2-B on serines/ threonines, whereas depletion of 4␤-phorbol 12-myristate 13-acetate-sensitive protein kinase Cs does not. ERKs 1 and 2 phosphorylate SH2-B␤ primarily on Ser-96 in vitro. However, NGF still stimulates serine/threonine phosphorylation of SH2-B␤(S96A). SH2-B␤(S96A), like wildtype SH2-B␤, enhances NGF-induced neurite outgrowth. In contrast, SH2-B␤(R555E) containing a defective SH2 domain blocks NGF-induced neurite outgrowth and displays greatly reduced phosphorylation on serines/threonines in response to NGF. SH2-B␤(R555E), like wild-type SH2-B␤, associates with the plasma membrane, suggesting that the dominant negative effect of SH2-B␤(R555E) cannot be explained by an abnormal subcellular distribution. In summary, NGF stimulates phosphorylation of SH2-B on serines/ threonines by kinases downstream of MEK, which may be important for NGF-mediated neuronal differentiation and survival.

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Interaction of two proline-rich sequences of cell adhesion kinase β with SH3 domains of p130Cas-related proteins and a GTPase-activating protein, Graf

Cited by 66 publications

References 45 publications

RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion

RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion

p210BCR/ABL-induced alteration of pre-mRNA splicing in primary human CD34+ hematopoietic progenitor cells

SH2-B, a Membrane-associated Adapter, Is Phosphorylated on Multiple Serines/Threonines in Response to Nerve Growth Factor by Kinases within the MEK/ERK Cascade

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