Protein Phosphorylation at Tyrosine in Normal and Transformed Cells

Cooper, Jonathan A.; Gould, Kathy; Hunter, Tony

doi:10.1007/978-1-4613-2583-3_4

RNA Tumor Viruses, Oncogenes, Human Cancer and AIDS: On the Frontiers of Understanding 1985

DOI: 10.1007/978-1-4613-2583-3_4

|View full text |Cite

Protein Phosphorylation at Tyrosine in Normal and Transformed Cells

Jonathan A. Cooper

Kathy Gould

Tony Hunter

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

1985

1990

Publication Types

Select...

Article3

Relationship

Self Cite0

Independent3

Authors

Journals

Cited by 3 publications

(4 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sequence comparison and in vitro mutagenesis studies indicate that the SM-FeSV v-fms gene has been activated as a result of one (35) or, at most, two (50) point mutations in the extracellular ligand-binding domain and a deletion of 50 amino acids at the C terminus of the protein that are replaced by 11 unrelated residues (9,50). A conserved tyrosine residue close to the C terminus, which is deleted in v-fms, has been implicated in activation of thefms protein, because of the analogy with pp6c-sr, which is regulated by phosphorylation at a tyrosine six residues from the C terminus (2,5,24,30). This hypothesis has been substantiated by analysis of mutants with point mutations at this site (36).…”

mentioning

confidence: 99%

“…In addition, we mutated Tyr-807, which is homologous to 5. Sensitivity of peptide "a" isolated from an in vitro tryptic phosphopeptide map to digestion with trypsin, chymotrypsin, and thermolysin.…”

mentioning

confidence: 99%

“…8), a position similar to Tyr-527 in pp60csrc (39). Phosphorylation of Tyr-527 in pp60csrc inhibits its kinase activity (2,5,24,30), and it is thought that pp6Oc-src is activated by dephosphorylation at this residue. Both Tyr-527 in pp6Oc-src and Tyr-969 in the CSF-1 receptor are deleted in the respective viral transforming proteins.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Identification of tyrosine 706 in the kinase insert as the major colony-stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the CSF-1 receptor in a murine macrophage cell line.

Geer¹,

Hunter²

1990

Mol. Cell. Biol.

View full text Add to dashboard Cite

The receptor for colony-stimulating factor 1 (CSF-1) is a ligand-activated protein-tyrosine kinase. It has been shown previously that the CSF-1 receptor is phosphorylated on serine in vivo and that phosphorylation on tyrosine can be induced by stimulation with CSF-1. We studied the phosphorylation of the CSF-1 receptor by using the BAC1.2F5 murine macrophage cell line, which naturally expresses CSF-1 receptors. Twodimensional tryptic phosphopeptide mapping showed that the CSF-1 receptor is phosphorylated on several different serine residues in vivo. Stimulation with CSF-1 at 3rC resulted in rapid phosphorylation on tyrosine at one major site and one or two minor sites. We identified the major site as Tyr-706. The identity of Tyr-706 was confirmed by mutagenesis. This residue is located within the kinase insert domain. There was no evidence that Tyr-973 (equivalent to Tyr-969 in the human CSF-1 receptor) was phosphorylated following CSF-1 stimulation. When cells were stimulated with CSF-1 at 4°C, additional phosphotyrosine-containing phosphopeptides were detected and the level of phosphorylation of the individual phosphotyrosine-containing phosphopeptides was substantially increased. In addition, we show that CSF-1 receptors are capable of autophosphorylation at six to eight major sites in vitro.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Identification of tyrosine 706 in the kinase insert as the major colony-stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the CSF-1 receptor in a murine macrophage cell line.

Geer¹,

Hunter²

1990

Mol. Cell. Biol.

View full text Add to dashboard Cite

show abstract

“…Otherwise, p42 phosphorylation may be limited by the action of protein-phosphotyrosine and protein-phosphoserine or protein-threonine phosphatases. Indeed, when PDGF is removed from the culture fluids by complexation with an excess of an antiserum to PDGF, pp42B is dephosphorylated almost completely within 20 min (5) reference 20). The precise precursor-product relationship among p42, pp42B, and pp42A is unclear.…”

mentioning

confidence: 99%

Major substrate for growth factor-activated protein-tyrosine kinases is a low-abundance protein.

Cooper¹,

Hunter²

1985

Mol. Cell. Biol.

View full text Add to dashboard Cite

A scarce, soluble, conserved protein was identified as the nonphosphorylated precursor of two related 42-kilodalton phosphoproteins that contain phosphotyrosine in mitogen-stimulated but not control fibroblasts.When cultures of resting fibroblasts are stimulated with many polypeptide or nonpeptide mitogens, there is an immediate increase in the phosphorylation of cell proteins at tyrosine (4,12,22). For example, the exposure of quiescent cultures of mouse 3T3 cells to epidermal growth factor or platelet-derived growth factor (PDGF) induces an approximate doubling of the protein phosphotyrosine content (4,12,22). An analysis of total cellular phosphoproteins by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis showed that about 25% of the total increase in tyrosine phosphorylation occurs through a fivefold increase in the phosphotyrosine content of proteins in the 40-to 42-kilodalton range (22). Proteins in this size range are among those recognized by antibodies specific for phosphotyrosine in extracts of PDGF-treated cells (13,14).Two-dimensional polyacrylamide gel electrophoresis revealed five phosphoproteins that have molecular masses between 40 and 45 kilodaltons and are rapidly phosphorylated in response to epidermal growth factor of PDGF (4, 21). Each contains significant amounts of phosphotyrosine and phosphoserine, and in four of the five phosphoproteins lesser amounts of phosphothreonine are detectable (4). It seems that these five phosphoproteins collectively contain most of the phosphotyrosine in proteins of ca. 42 kilodaltons and thus account for a significant fraction of the rapidly phosphorylated tyrosine in epidermal growth factor-or PDGF-treated cells. Two of the five phosphoproteins (pp42A and pp42B) have identical SDS gel mobilities and are closely related to each other, as determined by one-dimensional peptide mapping (11). pp42B and a variable number of the other four phosphoproteins are phosphorylated at tyrosine under a variety of other conditions that lead to cell growth, including exposure to other growth factors (such as fibroblast growth factor) and nonpeptide mitogens (such as some tumor promoters) and transformation with certain retroviruses (1, 5-7, 11, 17, 18, 21; unpublished results). The correlation between mitogen addition and the appearance of pp42B is consistent with the notion that this phosphoprotein might be important for some event in the mitogenic response.We suspected that pp42B arises from a precursor protein through the actions of growth factor-activated and transformation-activated protein-tyrosine kinases and protein-serine or protein-threonine kinases. (24) was added to the labeling medium to a final concentration of 0.83 to 1.0 nM for 5 to 15 min. Cell fractionation procedures have been described before (8). Labeled cell cultures were prepared for twodimensional gel electrophoresis as described before (6,15). Samples of 0.01 ml were analyzed on isoelectric focusing gels as described before (15), except that the urea concentration was 9.15 M and the am...

show abstract

Major Substrate for Growth Factor-Activated Protein-Tyrosine Kinases Is a Low-Abundance Protein

Cooper

Hunter

1985

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Protein Phosphorylation at Tyrosine in Normal and Transformed Cells

Cited by 3 publications

References 41 publications

Identification of tyrosine 706 in the kinase insert as the major colony-stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the CSF-1 receptor in a murine macrophage cell line.

Identification of tyrosine 706 in the kinase insert as the major colony-stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the CSF-1 receptor in a murine macrophage cell line.

Major substrate for growth factor-activated protein-tyrosine kinases is a low-abundance protein.

Major Substrate for Growth Factor-Activated Protein-Tyrosine Kinases Is a Low-Abundance Protein

Contact Info

Product

Resources

About