Tubulin is phosphorylated at tyrosine by pp60c-src in nerve growth cone membranes.

Matten, Wayne T.; Aubry, Muriel; West, J.Paige; Maness, Patricia E

doi:10.1083/jcb.111.5.1959

Cited by 140 publications

(73 citation statements)

References 78 publications

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“…Proteins that could clearly be delineated in both the DIGE analysis as having changed during capacitation, and in the phosphorylated-protein analysis as being tyrosine phosphorylated during capacitation, were identified by MALDI-TOF mass spectrometry and are presented in Table 2. From the perspective of this present study, it is significant to note that several of the proteins identified in Table 2 are known substrates for SRC-mediated phosphorylation, including enolase (Kralisz and Cierniewski, 2000), HSP90 (Hutchison et al, 1992) and tubulin (Matten et al, 1990).…”

Section: Inhibition Of Tyrosine Phosphorylation With Src Inhibitorsmentioning

confidence: 81%

Identification of SRC as a key PKA-stimulated tyrosine kinase involved in the capacitation-associated hyperactivation of murine spermatozoa

Baker

Hetherington

Aitken

2006

Journal of Cell Science

169

160

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Fertilization of the mammalian oocyte depends on the ability of spermatozoa to undergo a process known as capacitation as they ascend the female reproductive tract. A fundamental feature of this process is a marked increase in tyrosine phosphorylation by an unusual protein kinase A (PKA)-mediated pathway. To date, the identity of the intermediate PKA-activated tyrosine kinase driving capacitation is still unresolved. In this study, we have identified SRC as a candidate intermediate kinase centrally involved in the control of sperm capacitation. Consistent with this conclusion, the SRC kinase inhibitor SU6656 was shown to suppress both tyrosine phosphorylation and hyperactivation in murine spermatozoa. Moreover, SRC co-immunoprecipitated with PKA and this interaction was found to lead to an activating phosphorylation of SRC at position Y416. We have also used difference-in-2D-gel-electrophoresis (DIGE) in combination with mass spectrometry to identify a number of SRC substrates that become phosphorylated during capacitation including enolase, HSP90 and tubulin. Our data further suggest that the activation of SRC during capacitation is negatively controlled by C-terminal SRC kinase. The latter was localized to the acrosome and flagellum of murine spermatozoa by immunocytochemistry, whereas capacitation was associated with an inactivating serine phosphosphorylation of this inhibitory kinase.

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Section: Inhibition Of Tyrosine Phosphorylation With Src Inhibitorsmentioning

confidence: 81%

Identification of SRC as a key PKA-stimulated tyrosine kinase involved in the capacitation-associated hyperactivation of murine spermatozoa

Baker

Hetherington

Aitken

2006

Journal of Cell Science

169

160

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“…In this way, MAP2-bound Src in developing dendrites might be directed to regions of active microtubule dynamics, such as nerve growth cones, for participation in neuronal morphogenesis. ␣-and ␤-tubulins, the building blocks of microtubules, have been reported to be phosphorylated by pp60 c-Src at nerve growth cone membranes (65). Because soluble MAP2 associates with microfilaments, actin and actin-binding proteins could also be targeted by Src.…”

Section: Discussionmentioning

confidence: 99%

Regulated Association of Microtubule-associated Protein 2 (MAP2) with Src and Grb2: Evidence for MAP2 as a Scaffolding Protein

Lim

Halpain

2000

Journal of Biological Chemistry

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Microtubule-associated protein 2 (MAP2) and tau, which is involved in Alzheimer's disease, are major cytoskeletal proteins in neurons. These proteins are involved in microtubule assembly and stability. To further characterize MAP2, we took a strategy of identifying potential MAP2 binding partners. The low molecular weight MAP2c protein has 11 PXXP motifs that are conserved across species, and these PXXP motifs could be potential ligands for Src homology 3 (SH3) domains. We tested for MAP2 interaction with SH3 domain-containing proteins. All neuronal MAP2 isoforms bound specifically to the SH3 domains of c-Src and Grb2 in an in vitro glutathione S-transferase-SH3 pull-down assay. Interactions between endogenous proteins were confirmed by co-immunoprecipitation using brain lysate. All three proteins were also found co-expressed in neuronal cell bodies and dendrites. Surprisingly, the SH3 domainbinding site was mapped to the microtubule-binding domain that contains no PXXP motif. Src bound primarily the soluble, non-microtubule-associated MAP2c in vitro. This specific MAP2/SH3 domain interaction was inhibited by phosphorylation of MAP2c by the mitogenactivated protein kinase extracellular signal-regulated kinase 2 but not by protein kinase A. This phosphorylation-regulated association of MAP2 with proteins of intracellular signal transduction pathways suggests a possible link between cellular signaling and neuronal cytoskeleton, with MAP2 perhaps acting as a molecular scaffold upon which cytoskeleton-modifying proteins assemble and dissociate in response to neuronal activity.In the mammalian nervous system, the neuron-specific microtubule-associated protein MAP2 1 regulates microtubule dynamics (1) and is attributed with an important role in neurite outgrowth and dendrite development (2-6). MAP2 belongs to a family of heat stable microtubule-associated proteins found in eukaryotic cells. Other family members include MAP4, a ubiquitous protein, and tau, a neuronal protein involved in Alzheimer's disease (4, 5). Members of this family share a common microtubule-binding domain (MTBD) consisting of approximately 100 -130 amino acid residues near the carboxyl terminus of the molecule. The MTBD contains three or four tandem imperfect repeats of 18 amino acid residues separated by a variable inter-repeat region of approximately 12 amino acid residues (7).Recently, tau has been shown to bind the Src family of non-receptor tyrosine kinases (Src, Lyn, and Fyn (8)) and protein phosphatases PP1 and PP2A (9 -11). The interactions among PP1, PP2A, tau, and microtubules were postulated to regulate the phosphorylation state of tau, and alterations to these interactions could lead to the development of tauopathies seen in neurological diseases such as . This increasing body of evidence suggests that microtubule-based structural proteins like MAP2 and tau could play other physiological roles in addition to the regulation of microtubule assembly.Like tau, MAP2 is a phosphoprotein, and its cellular activities are regulated by phosphor...

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“…Little is known about the regulation ofthe formation ofruffled borders in osteoclasts. However, it is likely that reorganization of cytoskeletal proteins, such as actin, a-actinin, talin, and tubulin, takes place in activated osteoclasts (10), and tubulin has been shown to be a substrate for pp6O0 in normal brain cells (11,12). Tubulin, vinculin, talin, and the transmembrane receptor for fibronectin are substrates for pp60v in Rous sarcoma virus transformed cells, and some of these are localized to sites of cytoplasmic ruffling ( 13).…”

Section: Discussionmentioning

confidence: 99%

Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice.

Yoneda¹,

Lowe²,

Soriano³

et al. 1992

J. Clin. Invest.

531

396

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Targeted disruption of the c-src proto-oncogene in mice has shown that src expression is required for normal bone resorption, since the src-deficient mutants develop osteopetrosis. To evaluate the mechanisms by which src-deficiency affects osteoclast function, we treated src-deficient mice with the stimulants of bone resorption, IL-1, parathyroid hormone, and parathyroid hormone-related protein, and analyzed the effects by quantitative bone histomorphometry and electron microscopy. Increased numbers of multinucleated cells with the morphological characteristics of osteoclasts appeared on bone surfaces, but these cells did not form ruffled borders or normal resorption lacunae. To confirm these in vivo findings, we cultured src-mutant bone marrow cells on dentine slices in the presence of 1,25 dihydroxyvitamin D3. Increased numbers of multinucleated cells were formed, but unlike normal murine bone marrow cells, they did not form resorption pits. These results indicate that osteoclasts appear in the absence of pp6Or, but that pp6O C expression is required for mature osteoclasts to form ruffled borders and resorb bone. (J. Clin. Invest. 1992.

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Tubulin is phosphorylated at tyrosine by pp60c-src in nerve growth cone membranes.

Cited by 140 publications

References 78 publications

Identification of SRC as a key PKA-stimulated tyrosine kinase involved in the capacitation-associated hyperactivation of murine spermatozoa

Identification of SRC as a key PKA-stimulated tyrosine kinase involved in the capacitation-associated hyperactivation of murine spermatozoa

Regulated Association of Microtubule-associated Protein 2 (MAP2) with Src and Grb2: Evidence for MAP2 as a Scaffolding Protein

Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice.

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