Isoforms of JSAP1 scaffold protein generated through alternative splicing

Ito, Michihiko; Akechi, Mizuho; Hirose, Ryo; Ichimura, Michio; Takamatsu, Nobuhiko; Xu, Ping; Nakabeppu, Yusaku; Shiba, Tadayoshi; Yamamoto, Ken; Yoshioka, Katsuji

doi:10.1016/s0378-1119(00)00335-8

Cited by 32 publications

(28 citation statements)

References 19 publications

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“…JLP, which is expressed fairly ubiquitously, shares significant sequence identity with JNK/stress-activated protein kinase-associated protein 1 [JSAP1, or JNK-interacting protein 3 (JIP3)], a scaffold protein for JNK cascades (Ito et al, 1999;Ito et al, 2000;Kelkar et al, 2000). Nguyen et al (2005) showed that JLP physically interacts with kinesin light chain 1, and Kashef et al (2005) showed that it interacts with G α13 , the α-subunit of the heteromeric G 13 protein.…”

Section: Introductionmentioning

confidence: 99%

Ablation of the scaffold protein JLP causes reduced fertility in male mice

et al. 2008

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1 AbstractThe specific and efficient activation of mitogen-activated protein kinase (MAPK) signaling modules is mediated, at least in part, by scaffold proteins. c-Jun NH 2 -terminal kinase (JNK)-associated leucine zipper protein (JLP) was identified as a scaffold protein for JNK and p38 MAPK signaling modules. JLP is expressed nearly ubiquitously and is involved in intracellular signaling pathways, such as the G α13 and Cdo-mediated pathway, in vitro. To date, however, JLP expression has not been analyzed in detail, nor are its physiological functions well understood. Here we investigated the expression of JLP in the mouse testis during development.Of the tissues examined, JLP was strongest in the testis, with the most intense staining in the elongated spermatids. Since the anti-JLP antibody used in this study can recognize both JLP and sperm-associated antigen 9 (SPAG9), a splice variant of JLP that has been studied extensively in primates, we also examined its expression in macaque testis samples. Our results indicated that in mouse and primate testis, the isoform expressed at the highest level was JLP, not SPAG9. We also investigated the function of JLP by disrupting the Jlp gene in mice, and found that the male homozygotes were subfertile. Taken together, these observations may suggest that JLP plays an important role in testis during development, especially in the production of functionally normal spermatozoa.

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Section: Introductionmentioning

confidence: 99%

Ablation of the scaffold protein JLP causes reduced fertility in male mice

et al. 2008

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“…These MAPKKs then phosphorylate the threonine and tyrosine residues in MAPKs. This three-component module could be assembled together by scaffold proteins that ensure the efficiency and specificity of each individual MAPK pathway [8][9][10] . The activated MAPKs then translocate to the nucleus and phosphorylate scores of target proteins, including many transcription factors.…”

Section: Introductionmentioning

confidence: 99%

ATM and ATR: Sensing DNA damage

Yang¹,

Xu²,

Huang³

et al. 2004

WJG

119

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Cellular response to genotoxic stress is a very complex process, and it usually starts with the "sensing" or "detection" of the DNA damage, followed by a series of events that include signal transduction and activation of transcription factors. The activated transcription factors induce expressions of many genes which are involved in cellular functions such as DNA repair, cell cycle arrest, and cell death. There have been extensive studies from multiple disciplines exploring the mechanisms of cellular genotoxic responses, which have resulted in the identification of many cellular components involved in this process, including the mitogen-activated protein kinases (MAPKs) cascade. Although the initial activation of protein kinase cascade is not fully understood, human protein kinases ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) are emerging as potential sensors of DNA damage. Current progresses in ATM/ATR research and related signaling pathways are discussed in this review, in an effort to facilitate a better understanding of genotoxic stress response.

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“…JLP is broadly expressed, and is structurally related to JNK/stress-activated protein kinase-associated protein 1 (JSAP1 or JNK-interacting protein 3), a scaffold protein for JNK cascades (7)(8)(9).…”

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The Scaffold Protein c-Jun NH2-Terminal Kinase-associated Leucine Zipper Protein Regulates Cell Migration through Interaction with the G Protein G 13

Davaakhuu

Tuvshintugs

Endo

et al. 2008

Journal of Biochemistry

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Scaffold proteins for MAP kinase (MAPK) signalling modules play an important role in the specific and efficient signal transduction of the relevant MAPK cascades. Here, we investigated the function of the scaffolding protein c-Jun NH 2 -terminal kinase (JNK)-associated leucine zipper protein (JLP) by depleting it in cultured cells using a short hairpin RNA (shRNA) against human JLP. HeLa and DLD-1 cells stably expressing the shRNA showed a defect in cell migration. The re-expression of fulllength shRNA-resistant mouse JLP rescued the impaired cell migration of the JLPdepleted HeLa cells; whereas, a C-terminal deletion mutant of mouse JLP, which failed to bind the G protein G a13 , showed little or no effect on the cell migration defect. Furthermore, although a constitutively active G a13 enhanced the migration of control HeLa cells, the G a13 -induced cell migration was significantly suppressed in the JLP-depleted HeLa cells. Taken together, these results suggest that JLP regulates cell migration through an interaction with G a13 .Key words: cell migration, MAP kinase, p38, RNA interference, scaffold protein.Abbreviations: DMEM, Dulbecco's modified Eagle's medium; EDTA, ethylenediaminetetraacetic acid; GST, glutathione S-transferase; HEK, human embryonic kidney; JLP, JNK-associated leucine zipper protein; JNK, c-Jun NH2-terminal kinase; JSAP1, JNK/stress-activated protein kinase-associated protein 1; KD, knockdown; MAPK, MAP kinase; PCNA, proliferating cell nuclear antigen; PCR, polymerase chain reaction; shRNA, short hairpin RNA.MAP kinase (MAPK) cascades transmit signals through the sequential phosphorylation and activation of threetier kinase modules, consisting of MAPK kinase kinase, MAPK kinase and MAPK. Mammalian MAPK signalling pathways play a key role in multiple cellular functions, such as proliferation, migration and apoptosis (1, 2). The specificity of MAPK signalling is mediated, at least in part, by scaffold proteins. Scaffold proteins for MAPK cascades organize the MAPK signalling components into functional modules, thereby enabling the efficient activation of specific MAPK pathways (3-5). The scaffolding complexes also protect the signalling components within the relevant MAPK modules from undesired activation by other signalling molecules in cells.c-Jun NH 2 -terminal kinase (JNK)-associated leucine zipper protein (JLP) was originally identified as a binding protein for the transcription factor Max, and further biochemical study indicated that JLP functions as a scaffold protein for the JNK and p38 MAPK signalling modules (6). JLP is broadly expressed, and is structurally related to JNK/stress-activated protein kinase-associated protein 1 (JSAP1 or JNK-interacting protein 3), a scaffold protein for JNK cascades (7-9).Studies of JLP have mainly focused on identifying its interacting proteins, which include kinesin light chain 1 and G a13 , the a-subunit of the heteromeric G 13 protein (10,11). JLP has also been reported to play an important role in myogenesis by interacting with the cell-surface p...

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Isoforms of JSAP1 scaffold protein generated through alternative splicing

Cited by 32 publications

References 19 publications

Ablation of the scaffold protein JLP causes reduced fertility in male mice

Ablation of the scaffold protein JLP causes reduced fertility in male mice

ATM and ATR: Sensing DNA damage

The Scaffold Protein c-Jun NH2-Terminal Kinase-associated Leucine Zipper Protein Regulates Cell Migration through Interaction with the G Protein G 13

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