scholarly journals The Docking Protein Cas Links Tyrosine Phosphorylation Signaling to Elongation of Cerebellar Granule Cell Axons

2006 ◽  
Vol 17 (7) ◽  
pp. 3187-3196 ◽  
Author(s):  
Jinhong Huang ◽  
Ryuichi Sakai ◽  
Teiichi Furuichi
Keyword(s):  
Tyrosine Phosphorylation ◽  
Granule Cell ◽  
Tyrosine Kinases ◽  
Granule Cells ◽  
Protein Tyrosine Kinases ◽  
Axon Elongation ◽  
Axon Extension ◽  
Family Protein ◽  
Docking Protein ◽  
The Brain

Crk-associated substrate (Cas) is a tyrosine-phosphorylated docking protein that is indispensable for the regulation of the actin cytoskeletal organization and cell migration in fibroblasts. The function of Cas in neurons, however, is poorly understood. Here we report that Cas is dominantly enriched in the brain, especially the cerebellum, of postnatal mice. During cerebellar development, Cas is highly tyrosine phosphorylated and is concentrated in the neurites and growth cones of granule cells. Cas coimmunoprecipitates with Src family protein tyrosine kinases, Crk, and cell adhesion molecules and colocalizes with these proteins in granule cells. The axon extension of granule cells is inhibited by either RNA interference knockdown of Cas or overexpression of the Cas mutant lacking the YDxP motifs, which are tyrosine phosphorylated and thereby interact with Crk. These findings demonstrate that Cas acts as a key scaffold that links the proteins associated with tyrosine phosphorylation signaling pathways to the granule cell axon elongation.

scholarly journals Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase.

1994 ◽  
Vol 14 (2) ◽  
pp. 1308-1321 ◽  
Author(s):  
M Autero ◽  
J Saharinen ◽  
T Pessa-Morikawa ◽  
M Soula-Rothhut ◽  
C Oetken ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Lymphocyte Activation ◽  
Sh2 Domain ◽  
Protein Tyrosine Kinases ◽  
Phosphotyrosine Phosphatase ◽  
Intact Cells ◽  
Tyrosine Residues ◽  
Family Protein ◽  
Ptpase Activity

Src family protein tyrosine kinases (PTKs) play an essential role in antigen receptor-initiated lymphocyte activation. Their activity is largely regulated by a negative regulatory tyrosine which is a substrate for the activating action of the CD45 phosphotyrosine phosphatase (PTPase) or, conversely, the suppressing action of the cytosolic p50csk PTK. Here we report that CD45 was phosphorylated by p50csk on two tyrosine residues, one of them identified as Tyr-1193. This residue was not phosphorylated by T-cell PTKs p56lck and p59fyn. Tyr-1193 was phosphorylated in intact T cells, and phosphorylation increased upon treatment with PTPase inhibitors, indicating that this tyrosine is a target for a constitutively active PTK. Cotransfection of CD45 and csk into COS-1 cells caused tyrosine phosphorylation of CD45 in the intact cells. Tyrosine-phosphorylated CD45 bound p56lck through the SH2 domain of the kinase. Finally, p50csk-mediated phosphorylation of CD45 caused a severalfold increase in its PTPase activity. Our results show that direct tyrosine phosphorylation of CD45 can affect its activity and association with Src family PTKs and that this phosphorylation could be mediated by p50csk. If this is also true in the intact cells, it adds a new dimension to the physiological function of p50csk in T lymphocytes.

scholarly journals Tyrosine Phosphorylation of Pyk2 Is Selectively Regulated by Fyn During TCR Signaling

1997 ◽  
Vol 185 (7) ◽  
pp. 1253-1260 ◽  
Author(s):  
Dapeng Qian ◽  
Sima Lev ◽  
Nicolai S.C. van Oers ◽  
Ivan Dikic ◽  
Joseph Schlessinger ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinases ◽  
Tcr Signaling ◽  
Family Protein ◽  
Tcr Signal Transduction

The Src family protein tyrosine kinases (PTKs), Lck and Fyn, are coexpressed in T cells and perform crucial functions involved in the initiation of T cell antigen receptor (TCR) signal transduction. However, the mechanisms by which Lck and Fyn regulate TCR signaling are still not completely understood. One important question is whether Lck and Fyn have specific targets or only provide functional redundancy during TCR signaling. We have previously shown that Lck plays a major role in the tyrosine phosphorylation of the TCR-ζ chain and the ZAP-70 PTK. In an effort to identify the targets that are specifically regulated by Fyn, we have studied the tyrosine phosphorylation of Pyk2, a recently discovered new member of the focal adhesion kinase family PTK. We demonstrated that Pyk2 was rapidly tyrosine phosphorylated following TCR stimulation. TCR-induced tyrosine phosphorylation of Pyk2 was selectively dependent on Fyn but not Lck. Moreover, in heterologous COS-7 cells, coexpression of Pyk2 with Fyn but not Lck resulted in substantial increases in Pyk2 tyrosine phosphorylation. The selective regulation of Pyk2 tyrosine phosphorylation by Fyn in vivo correlated with the preferential phosphorylation of Pyk2 by Fyn in vitro. Our results demonstrate that Pyk2 is a specific target regulated by Fyn during TCR signaling.

scholarly journals Efficient generation of reciprocal signals by inhibition

2012 ◽  
Vol 107 (9) ◽  
pp. 2453-2462 ◽  
Author(s):  
Sung-min Park ◽  
Esra Tara ◽  
Kamran Khodakhah
Keyword(s):  
Purkinje Cells ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Cell Activity ◽  
Common Mechanism ◽  
Input Output ◽  
Firing Rates ◽  
Neuronal Computation ◽  
The Brain

Reciprocal activity between populations of neurons has been widely observed in the brain and is essential for neuronal computation. The different mechanisms by which reciprocal neuronal activity is generated remain to be established. A common motif in neuronal circuits is the presence of afferents that provide excitation to one set of principal neurons and, via interneurons, inhibition to a second set of principal neurons. This circuitry can be the substrate for generation of reciprocal signals. Here we demonstrate that this equivalent circuit in the cerebellar cortex enables the reciprocal firing rates of Purkinje cells to be efficiently generated from a common set of mossy fiber inputs. The activity of a mossy fiber is relayed to Purkinje cells positioned immediately above it by excitatory granule cells. The firing rates of these Purkinje cells increase as a linear function of mossy fiber, and thus granule cell, activity. In addition to exciting Purkinje cells positioned immediately above it, the activity of a mossy fiber is relayed to laterally positioned Purkinje cells by a disynaptic granule cell → molecular layer interneuron pathway. Here we show in acutely prepared cerebellar slices that the input-output relationship of these laterally positioned Purkinje cells is linear and reciprocal to the first set. A similar linear input-output relationship between decreases in Purkinje cell firing and strength of stimulation of laterally positioned granule cells was also observed in vivo. Use of interneurons to generate reciprocal firing rates may be a common mechanism by which the brain generates reciprocal signals.

Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases

1992 ◽  
Vol 12 (5) ◽  
pp. 2315-2321
Author(s):  
M A Campbell ◽  
B M Sefton
Keyword(s):  
B Cells ◽  
B Cell ◽  
Tyrosine Kinases ◽  
B Lymphocyte ◽  
Protein Tyrosine Kinases ◽  
Cell Type ◽  
Protein Tyrosine ◽  
Membrane Immunoglobulin ◽  
Family Protein

Treatment of B lymphocytes with antibodies to membrane immunoglobulin (Ig) stimulates protein tyrosine phosphorylation. We have examined the phosphorylation in vitro of proteins associated with membrane Ig. The Src family protein tyrosine kinases p53/56lyn, p59fyn, and p56lck are associated with membrane Ig in spleen B cells and B-cell lines and undergo phosphorylation in vitro. The pattern of expression of Src family protein tyrosine kinases in B cells varied. Our studies suggest that multiple kinases can potentially interact with membrane Ig and that within any one B-cell type, all of the Src family kinases expressed can be found in association with membrane Ig. We also observed that the Ig-associated Ig alpha protein, multiple forms of Ig beta, and proteins of 100 and 25 kDa were tyrosine phosphorylated in vitro. The 100- and 25-kDa proteins remain unidentified.

scholarly journals Transformation of NIH 3T3 fibroblasts by an activated form of p59hck.

1989 ◽  
Vol 9 (6) ◽  
pp. 2724-2727 ◽  
Author(s):  
S F Ziegler ◽  
S D Levin ◽  
R M Perlmutter
Keyword(s):  
Tyrosine Kinases ◽  
Soft Agar ◽  
Protein Tyrosine Kinases ◽  
3T3 Fibroblasts ◽  
Family Protein ◽  
Cloning Assay ◽  
Transforming Activity ◽  
Nih 3T3 ◽  
Soft Agar Cloning ◽  
Phenylalanine Residue

Phosphorylation of a tyrosine residue near the carboxy terminus of src-family protein tyrosine kinases is believed to regulate the biological activity of these gene products. Conversion of this tyrosine in p59hck (Tyr-501) to a phenylalanine residue by using oligonucleotide-directed mutagenesis yielded a product (p59hckF501) with very potent transforming activity. Quantitative analysis by a soft-agar cloning assay revealed that p59hckF501 was more than 100-fold more effective than a closely related transforming element, p56lckF505, in colony formation. Cells bearing p59hckF501 had increased levels of protein phosphotyrosine. The ability of p59hckF501 to transform NIH 3T3 cells was abolished by a second mutation believed to destroy the ATP-binding domain.

scholarly journals Regulation of Mouse PECAM-1 Tyrosine Phosphorylation by the Src and Csk Families of Protein-tyrosine Kinases

1998 ◽  
Vol 273 (25) ◽  
pp. 15765-15772 ◽  
Author(s):  
Ming Yu Cao ◽  
Maria Huber ◽  
Nicole Beauchemin ◽  
Julie Famiglietti ◽  
Steven M. Albelda ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinases ◽  
Protein Tyrosine

scholarly journals Involvement of Src Family Protein Tyrosine Kinases in Ca 2+ Sensitization of Coronary Artery Contraction Mediated by a Sphingosylphosphorylcholine-Rho-Kinase Pathway

2002 ◽  
Vol 91 (10) ◽  
pp. 953-960 ◽  
Author(s):  
Fumiaki Nakao ◽  
Sei Kobayashi ◽  
Kimiko Mogami ◽  
Yoichi Mizukami ◽  
Satoshi Shirao ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Tyrosine Kinases ◽  
Rho Kinase ◽  
Protein Tyrosine Kinases ◽  
Protein Tyrosine ◽  
Family Protein ◽  
Kinase Pathway
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