首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
We established Jurkat transfectants that overexpress Pyk2 or its mutants, K457A (lysine 457 was mutated to alanine), Pyk2-Y402F (tyrosine 402 to phenylalanine), and Pyk2-Y881F to investigate the role of Pyk2 in T cell activation. Pyk2 as well as kinase-inactive Pyk2-K457A, was phosphorylated at tyrosine residues 402, 580, and 881 upon T cell antigen receptor cross-linking, indicating that these residues are phosphorylated by other tyrosine kinase(s). However, no tyrosine phosphorylation of Pyk2-Y402F was detected while more than 60% of the tyrosine phosphorylation was observed in Pyk2-Y881F. Pyk2-Y402F inhibited the activation of endogenous Pyk2. The degree of activation of both c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase but not extracellular signal-regulated protein kinase after concurrent ligation of T cell antigen receptor and CD28 was reduced by more than 50% in the clones expressing Pyk2-Y402F. Consistent with this inhibition, IL-2 production was significantly diminished in the Pyk2-Y402F-expressing clones. Furthermore, we found that Pyk2, when overexpressed, associates with Zap70 and Vav. Taken together, these findings suggest that Pyk2 is involved in the activation of T cells through its tyrosine 402.  相似文献   

2.
Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase (FAK) family of non-receptor tyrosine kinases and plays an important role in diverse cellular events downstream of the integrin-family of receptors, including cell migration, proliferation and survival. Here, we have identified a novel role for Src kinase in priming Pyk2 phosphorylation and subsequent activation upon cell attachment on the integrin-ligand fibronectin. By using complementary methods, we show that Src activity is indispensable for the initial Pyk2 phosphorylation on the Y402 site observed in response to cell attachment. In contrast, the initial fibronectin-induced autophosphorylation of FAK in the homologous Y397 site occurs in a Src-independent manner. We demonstrate that the SH2-domain of Src is required for Src binding to Pyk2 and for Pyk2 phosphorylation at sites Y402 and Y579. Moreover, Y402 phosphorylation is a prerequisite for the subsequent Y579 phosphorylation. While this initial phosphorylation of Pyk2 by Src is independent of Pyk2 kinase activity, subsequent autophosphorylation of Pyk2 in trans is required for full Pyk2 phosphorylation and activation. Collectively, our studies reveal a novel function of Src in priming Pyk2 (but not FAK) phosphorylation and subsequent activation downstream of integrins, and shed light on the signaling events that regulate the function of Pyk2.  相似文献   

3.
Activation of tyrosine kinases is believed to play a central role in angiotensin II (AngII) signaling. Here, we have investigated whether a tyrosine kinase, PYK2, is functionally involved in AngII-induced c-Jun N-terminal kinase (JNK) activation in vascular smooth muscle cells (VSMCs). Adenovirus expressing PYK2 kinase-inactive mutant K457A or a tyrosine phosphorylation site mutant Y402F was transfected in VSMCs. AngII-induced JNK phosphorylation was markedly enhanced by K457A, whereas it was suppressed by Y402F. Protein synthesis induced by AngII was also enhanced by K457A and inhibited by Y402F. In this regard, K457A suppressed PYK2 kinase activation by AngII, whereas it enhanced AngII-induced PYK2 Tyr(402) phosphorylation. By contrast, Y402F inhibited PYK2 Tyr(402) phosphorylation, whereas it markedly enhanced AngII-induced PYK2 kinase activation. Thus, we conclude that PYK2 kinase activity negatively regulates JNK activation and protein synthesis, whereas Tyr(402) phosphorylation positively regulates these events in AngII-stimulated VSMCs, suggesting a unique role of PYK2 in mediating vascular remodeling.  相似文献   

4.
The calcium-dependent proline-rich tyrosine kinase Pyk2 is activated by tyrosine phosphorylation, associates with focal adhesion proteins, and has been linked to proliferative and migratory responses in a variety of mesenchymal and epithelial cell types. Full Pyk2 activation requires phosphorylation at functionally distinct sites, including autophosphorylation site Tyr-402 and catalytic domain site Tyr-580, though the mechanisms involved are unclear. The pathways mediating Pyk2 phosphorylation at Tyr-402 and Tyr-580 were therefore investigated. Both sites were rapidly and transiently phosphorylated following cell stimulation by Ang II or LPA. However, only Tyr-580 phosphorylation was rapidly enhanced by intracellular Ca(2+) release, or inhibited by Ca(2+) depletion. Conversely, Tyr-402 phosphorylation was highly sensitive to inhibition of actin stress fibers, or of Rho kinase (ROK), an upstream regulator of stress fiber assembly. Ang II also induced a delayed (30-60 min) secondary phosphorylation peak occurring at Tyr-402 alone. Unlike the homologous focal adhesion kinase (FAK), Pyk2 phosphorylation was sensitive neither to the Src inhibitor PP2, nor to truncation of its N-terminal region, which contains a putative autoinhibitory FERM domain. These results better define the mechanisms involved in Pyk2 activation, demonstrating that autophosphorylation is ROK- and stress fiber-dependent, while transphosphorylation within the kinase domain is Ca(2+)-dependent and Src-independent in intestinal epithelial cells. This contrasts with the tight sequential coupling of phosphorylation seen in FAK activation, and further underlines the differences between these closely related kinases.  相似文献   

5.
G-protein-coupled receptor agonists (GPCAs) cause functional responses in endothelial cells including secretion, proliferation, and altering monolayer permeability. These events are mediated in part by activation of the p42/44 mitogen-activated protein kinase (MAPK) cascade. The cytosolic tyrosine kinase Pyk2 is postulated to link GPCA-induced changes in intracellular calcium to activation of the MAP kinase cascade. We have investigated the regulation of Pyk2 in human umbilical vein endothelial cells in response to GPCAs and show that (1) thrombin, a PAR-1 peptide, and histamine cause rapid concentration- and time-dependent phosphorylation on tyrosines 402 (Src kinase binding site), 881 (Grb2 binding site), and 580 (an autophosphorylation site), (2) thrombin-stimulated phosphorylation is dependent on intracellular calcium and independent of PKC and PI-3 kinase, and (3) inhibition of Src kinases has no significant effect on thrombin-stimulated phosphorylation, implying that tyrosine phosphorylation of Pyk2 is independent of Src binding.  相似文献   

6.
The epidermal growth factor receptor (EGFR) and the non-receptor protein tyrosine kinases Src and Pyk2 have been implicated in linking a variety of G-protein-coupled receptors (GPCR) to the mitogen-activated protein (MAP) kinase signaling cascade. In this report we apply a genetic strategy using cells isolated from Src-, Pyk2-, or EGFR-deficient mice to explore the roles played by these protein tyrosine kinases in GPCR-induced activation of EGFR, Pyk2, and MAP kinase. We show that Src kinases are critical for activation of Pyk2 in response to GPCR-stimulation and that Pyk2 and Src are essential for GPCR-induced tyrosine phosphorylation of EGFR. By contrast, Pyk2, Src, and EGFR are dispensable for GPCR-induced activation of MAP kinase. Moreover, GPCR-induced MAP kinase activation is normal in fibroblasts deficient in both Src and Pyk2 (Src-/-Pyk2-/- cells) as well as in fibroblasts deficient in all three Src kinases expressed in these cells (Src-/-Yes-/-Fyn-/- cells). Finally, experiments are presented demonstrating that, upon stimulation of GPCR, activated Pyk2 forms a complex with Src, which in turn phosphorylates EGFR directly. These experiments reveal a role for Src kinases in Pyk2 activation and a role for Pyk2 and Src in tyrosine phosphorylation of EGFR following GPCR stimulation. In addition, EGFR, Src family kinases, and Pyk2 are not required for linking GPCRs with the MAP kinase signaling cascade.  相似文献   

7.
Pyk2 was identified as a Ca2+-dependent kinase, however, the regulation of Pyk2 by Ca2+ in T cells remains controversial. We found that Ca2+ mobilization preferentially induced Pyk2 phosphorylation in cytotoxic T lymphocytes (CTL). Furthermore, Pyk2 phosphorylation in CTL was not absolutely Ca2+ dependent but relied on the strength of T cell receptor stimulation. Ionomycin-stimulated Pyk2 phosphorylation did not require calmodulin activity, because phosphorylation was not inhibited by the calmodulin inhibitor W7, and we detected no Ca2+-regulated association between Pyk2 and calmodulin. Ca2+-stimulated Pyk2 phosphorylation was dependent on Src-family kinase activity, even at the Pyk2 autophosphorylation site. We sought to identify a Ca2+-regulated pathway that could trigger Pyk2 phosphorylation in T cells and found that ionomycin stimulated the production of reactive oxygen species and an H2O2 scavenger inhibited ionomycin-induced Pyk2 phosphorylation. Additionally, H2O2 induced strong Erk activation and ionomycin-stimulated Pyk2 phosphorylation was Erk dependent. These data support the conclusion that Ca2+ mobilization induces the production of reactive oxygen species, which in turn activate the Erk pathway, leading to Src-family kinase-dependent Pyk2 phosphorylation. Our data demonstrate that Pyk2 is not a Ca2+-dependent kinase in T cells but instead, increased intracellular Ca2+ induces Pyk2 phosphorylation through production of reactive oxygen species. These findings are consistent with the possibility that Pyk2 acts as an early sensor of numerous extracellular signals that trigger a Ca2+ flux and/or reactive oxygen species to amplify tyrosine phosphorylation signaling events.  相似文献   

8.
Src kinase activity is essential for osteoclast function   总被引:21,自引:0,他引:21  
Deletion of the c-src gene impairs osteoclast bone resorbing activity, causing osteopetrosis. Although it has been concluded that restoring only the Src adaptor function at least partly rescues the cell attachment and skeletal phenotypes, the contribution of Src kinase activity remains controversial. Src forms a complex with Pyk2 and Cbl after adhesion-induced stimulation of alpha(V)beta(3) integrin. To demonstrate the importance of the Pyk2-Src association in osteoclasts and to distinguish the contributions of the Src adaptor and kinase activities in cytoskeletal organization and osteoclast function, we expressed mutants of Src and Pyk2 in osteoclasts using adenovirus vectors. Eliminating the Src-binding site on Pyk2 (Pyk2(Y402F)) markedly inhibited bone resorption by osteoclast-like cells, whereas kinase-dead Pyk2 had little effect. Kinase-dead Src, unlike kinase-dead Pyk2, markedly inhibited the bone-resorbing activity of wild type osteoclasts and failed to significantly restore bone-resorbing activity to Src(-/-) osteoclast-like cells. Activation of Src kinase by overexpressing kinase-dead Csk failed to reverse the inhibitory effect of Pyk2(Y402F), suggesting that osteoclastic bone resorption requires both c-Src kinase activity and the targeting of Src kinase by Pyk2. Src-catalyzed phosphorylation of Cbl on Tyr-731 is reported to induce the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Expressing the Cbl(Y731F) mutant in osteoclasts markedly reduced their bone resorbing activity, suggesting that phosphorylation of Cbl(Y731) and the subsequent recruitment and activation of phosphatidylinositol 3-kinase may be critical signaling events downstream of Src in osteoclasts.  相似文献   

9.
Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase family and is highly expressed in brain and hematopoietic cells. Pyk2 plays diverse functions in cells, including the regulation of cell adhesion, migration, and cytoskeletal reorganization. In the brain, it is involved in the induction of long term potentiation through regulation of N-methyl-d-aspartate receptor trafficking. This occurs through the phosphorylation and activation of Src family tyrosine kinase members, such as Fyn, that phosphorylate GluN2B at Tyr(1472). Phosphorylation at this site leads to exocytosis of GluN1-GluN2B receptors to synaptic membranes. Pyk2 activity is modulated by phosphorylation at several critical tyrosine sites, including Tyr(402). In this study, we report that Pyk2 is a substrate of striatal-enriched protein-tyrosine phosphatase (STEP). STEP binds to and dephosphorylates Pyk2 at Tyr(402). STEP KO mice showed enhanced phosphorylation of Pyk2 at Tyr(402) and of the Pyk2 substrates paxillin and ASAP1. Functional studies indicated that STEP opposes Pyk2 activation after KCl depolarization of cortical slices and blocks Pyk2 translocation to postsynaptic densities, a key step required for Pyk2 activation and function. This is the first study to identify Pyk2 as a substrate for STEP.  相似文献   

10.
Protein tyrosine kinases are critical for the function of CD28 in T cells. We examined whether the tyrosine kinases Pyk2 and Fak (members of the focal adhesion kinase family) are involved in CD28 signaling. We found that ligating CD28 in Jurkat T cells rapidly increases the tyrosine phosphorylation of Pyk2 but not of Fak. Paxillin, a substrate for Pyk2 and Fak, was not tyrosine-phosphorylated after CD28 ligation. CD28-induced tyrosine phosphorylation of Pyk2 was markedly reduced in the absence of external Ca2+. Previous studies have shown that the T cell antigen receptor (TCR) induces tyrosine phosphorylation of Pyk2. In this report, the concurrent ligation of CD28 and TCR increased tyrosine phosphorylation of Pyk2; however, the extent of phosphorylation by both receptors was equivalent to the sum of that induced by each receptor alone. The Syk/Zap inhibitor piceatannol blocked CD28, and TCR induced tyrosine phosphorylation of Pyk2, suggesting that Syk/Zap is involved in Pyk2 phosphorylation. In contrast, the phosphatidylinositol 3-kinase inhibitor wortmannin blocked TCR- but not CD28-induced phosphorylation of Pyk2, suggesting that CD28 and TCR activate distinct pathways to induce tyrosine phosphorylation of Pyk2. Notably, depleting phorbol 12-myristate 13-acetate-sensitive protein kinase C did not block CD28- and CD3-induced tyrosine phosphorylation of Pyk2. These data provide evidence for the involvement of Pyk2 in the CD28 signaling cascade and suggest that neither Fak nor paxillin is involved in the signaling pathways of CD28.  相似文献   

11.
Interleukin-7 (IL-7) receptor signaling begins with activation of the Janus tyrosine kinases Jak1 and Jak3, which are associated with the receptor complex. To identify potential targets of these kinases, we examined Pyk2 (a member of the focal adhesion kinase family) using an IL-7-dependent murine thymocyte line, D1. We demonstrate that stimulation of D1 (or normal pro-T) cells by IL-7 rapidly increased tyrosine phosphorylation and enzymatic activity of Pyk2, with kinetics slightly lagging that of Jak1 and Jak3 phosphorylation. Conversely, IL-7 withdrawal resulted in a marked decrease of Pyk2 phosphorylation. Pyk2 was found to be physically associated with Jak1 prior to IL-7 stimulation and to increase its association with IL-7Ralpha chain following IL-7 stimulation. Pyk2 appeared to be involved in cell survival, because antisense Pyk2 accelerated the cell death process. Activation of Pyk2 via the muscarinic and nicotinic receptors using carbachol or via intracellular Ca(2+) rise using ionomycin/phorbol myristate acetate promoted survival in the absence of IL-7. These data support a role for Pyk2 in coupling Jak signaling to the trophic response.  相似文献   

12.
13.
We previously showed that stimulation of muscarinic acetylcholine receptors (mAChR) by carbachol (Cch) caused a time- and dose-dependent increase of mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERK) phosphorylation in thyroid epithelial cells. In this study, we demonstrated that mAChR stimulation also induced a time-dependent increase in the tyrosine phosphorylation of proline-rich tyrosine kinase 2 (Pyk2), which was prevented by pretreatment of thyroid epithelial cells with the specific Src-family tyrosine kinase inhibitor PP2. Besides, phosphorylation of Pyk2 was attenuated by chelation of extracellular Ca(2+) or inhibition of phospholipase C (PLC), and was evoked by thapsigargin, a specific microsomal Ca(2+)-ATPase inhibitor. Incorporation of Pyk2 antisense oligonucleotides in thyroid epithelial cells to down-regulated Pyk2 expression or pretreatment of cells with the Ca(2+)/calmodulin protein kinase II (CaM kinase II) inhibitor KN-62 significantly reduced Cch-induced MAPK/ERK phosphorylation. In addition, Cch-induced MAPK/ERK phosphorylation was partially inhibited by LY294002 and wortmannin, two selective inhibitors of phosphatidylinositol 3-kinase (PI3K), tyrphostin AG1478, a specific inhibitor of epidermal growth factor receptor (EGFR) kinase, and (-)-perillic acid, a post-translational inhibitor of small G-proteins isoprenylation. Taken together, our data suggest that Pyk2, CaM kinase II and Src-family tyrosine kinases are key molecules for the activation of MAPK/ERK cascade through the EGFR/Ras/Raf pathway in thyroid epithelial cells in response to mAChR stimulation.  相似文献   

14.
The G protein-coupled receptor agonistsangiotensin II (ANG II) and lysophosphatidic acid (LPA) rapidly inducetyrosine phosphorylation of the cytosolic proline-rich tyrosine kinase2 (Pyk2) in IEC-18 intestinal epithelial cells. The combined Pyk2tyrosine phosphorylation induced by phorbol 12,13-dibutyrate, a directagonist of protein kinase C (PKC), and ionomycin, a Ca2+ionophore, was equal to that induced by ANG II. Inhibition of eitherPKC or Ca2+ signaling attenuated the effect of ANG II andLPA, although simultaneous inhibition of both pathways failed tocompletely abolish Pyk2 tyrosine phosphorylation. Cytochalasin D, whichdisrupts stress fibers, strongly inhibited the response of Pyk2 to ANGII or LPA. The distinct Rho-associated kinase (ROK) inhibitors HA-1077and Y-27632, as well as the Rho inhibitor Clostridiumbotulinum C3 exoenzyme, also significantly attenuated ANG II- andLPA-stimulated Pyk2 tyrosine phosphorylation. Simultaneous inhibitionof PKC, Ca2+, and either actin assembly or ROK completelyabolished the Pyk2 response. Together, these results show that ANG IIand LPA rapidly induce Pyk2 tyrosine phosphorylation in intestinalepithelial cells via separate Ca2+-, PKC-, and Rho-mediated pathways.

  相似文献   

15.
Recently we reported the activation MAPKs, MEK, and Rafs by electroconvulsive shock (ECS) in the rat hippocampus. However, the upstream pathways for the activation of Raf-MEK-MAPK cascade after ECS have not been studied yet. Since the proline-rich tyrosine kinase 2 (Pyk2) and Src were reported to be involved in the activation of the MAPKs in neuronal cells, we examined tyrosine phosphorylation and activation of Pyk2 in the rat hippocampus after ECS. ECS transiently increased the phosphorylation of Pyk2 at multiple tyrosine residues (Tyr-402, Tyr-580, and Tyr-881). The phosphorylations reached the peak at 1 min and returned to basal level by 10 min after ECS. At 1 min after ECS, the binding of Pyk2 to Src and Grb2, and of Grb2 to Ras increased. These results suggested that ECS activates Pyk2, which then transmits the signal to MAPK cascade via Src, Grb2, and Ras in the rat hippocampus.  相似文献   

16.
The hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH), utilizes multiple signaling pathways to activate extracellularly regulated mitogen-activated protein kinases (ERK1/2) in normal and immortalized pituitary gonadotrophs and transfected cells expressing the GnRH receptor. In immortalized hypothalamic GnRH neurons (GT1-7 cells), which also express GnRH receptors, GnRH, epidermal growth factor (EGF), and phorbol 12-myristate 13-acetate (PMA) caused marked phosphorylation of ERK1/2. This action of GnRH and PMA, but not that of EGF, was primarily dependent on activation of protein kinase C (PKC), and the ERK1/2 responses to all three agents were abolished by the selective EGF receptor kinase inhibitor, AG1478. Consistent with this, both GnRH and EGF increased tyrosine phosphorylation of the EGF receptor. GnRH and PMA, but not EGF, caused rapid phosphorylation of the proline-rich tyrosine kinase, Pyk2, at Tyr(402). This was reduced by Ca(2+) chelation and inhibition of PKC, but not by AG1478. GnRH stimulation caused translocation of PKC alpha and -epsilon to the cell membrane and enhanced the association of Src with PKC alpha and PKC epsilon, Pyk2, and the EGF receptor. The Src inhibitor, PP2, the C-terminal Src kinase (Csk), and dominant-negative Pyk2 attenuated ERK1/2 activation by GnRH and PMA but not by EGF. These findings indicate that Src and Pyk2 act upstream of the EGF receptor to mediate its transactivation, which is essential for GnRH-induced ERK1/2 phosphorylation in hypothalamic GnRH neurons.  相似文献   

17.
The role of protein kinase C (PKC) in tyrosine phosphorylation of the N‐methyl‐d ‐aspartate receptor (NMDAR) following transient cerebral ischemia was investigated. Transient (15 min) cerebral ischemia was produced in adult rats by four‐vessel occlusion and animals allowed to recover for 15 or 45 min. Following ischemia, tyrosine phosphorylation of NR2A and NR2B and activated Src‐family kinases (SFKs) and Pyk2 were increased in post‐synaptic densities (PSDs). Phosphorylation of NR2B on Y1472 by PSDs isolated from post‐ischemic forebrains was inhibited by the SFK specific inhibitor PP2, and by the PKC inhibitors GF109203X (GF), Gö6976 and calphostin C. Intravenous injection of GF immediately following the ischemic challenge resulted in decreased phosphorylation of NR1 on PKC phosphorylation sites and reduced ischemia‐induced increases in tyrosine phosphorylation of NR2A and NR2B without affecting the increase in total tyrosine phosphorylation of hippocampal proteins. Ischemia‐induced increases in activated Pyk2 and SFKs in PSDs, but not the translocation of PKC, Pyk2 or Src to the PSD, were also inhibited by GF. The inactive homologue of GF, bisindolylmaleimide V, had no effect on these parameters. The results are consistent with a role for PKC in the ischemia‐induced increase in tyrosine phosphorylation of the NMDAR, via a pathway involving Pyk2 and Src‐family kinases.  相似文献   

18.
alpha-Synuclein is a presynaptic protein involved in the pathogenesis of several neurodegenerative diseases, such as Parkinson's disease. Pyk2/related adhesion focal tyrosine kinase (RAFTK) tyrosine kinase is an upstream regulator of Src family kinases in the central nervous system that is involved in alpha-synuclein phosphorylation. The present study reports the cloning and characterization of a novel adaptor protein, Pyk2/RAFTK-associated protein (PRAP), that specifically binds to Pyk2/RAFTK and inhibits alpha-synuclein tyrosine phosphorylation. PRAP contains a coiled-coil domain, a pleckstrin homology domain, and a SH3 domain; the SH3 domain binds to the proline-rich domain of Pyk2/RAFTK. PRAP was observed to be present throughout the brain, including substantia nigra dopaminergic neurons, in which it localized to the cytoplasm. PRAP was found to function as a substrate for Src family kinases, such as c-Src or Fyn, but not for Pyk2/RAFTK. Hyperosmotic stress induced phosphorylation of tyrosine 125 of alpha-synuclein via Pyk2/RAFTK, which acted through Src family kinases. Such phosphorylation was inhibited by PRAP expression, suggesting that PRAP negatively regulates alpha-synuclein phosphorylation following cell stress. In conclusion, PRAP functions as a downstream target for Pyk2/RAFTK and plays a role in alpha-synuclein phosphorylation.  相似文献   

19.
RAFTK/Pyk2-mediated cellular signalling   总被引:1,自引:0,他引:1  
Intracellular signal transduction following extracellular ligation by a wide variety of surface molecules involves the activation and tyrosine phosphorylation of protein tyrosine kinases (PTKs). Tyrosine phosphorylation, controlled by the coordinated actions of protein tyrosine phosphatases (PTPs) and tyrosine kinases, is a critical regulatory mechanism for various physiological processes, including cell growth, differentiation, metabolism, cell cycle regulation and cytoskeleton function. The focal adhesion PTK family consists of the focal adhesion kinase (FAK) and the RAFTK/Pyk2 kinase (also known as CAK-beta and CADTK). RAFTK/Pyk2 can be activated by a variety of extracellular signals that elevate intracellular calcium concentration, and by stress signals. RAFTK/Pyk2 is expressed mainly in the central nervous system and in cells derived from hematopoietic lineages, while FAK is widely expressed in various tissues and links transmembrane integrin receptors to intracellular pathways. This review describes the role of RAFTK/Pyk2 in various signalling cascades and details the differential signalling by FAK and RAFTK/Pyk2.  相似文献   

20.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号