Amino‐terminal sequence determinants for substrate recognition by platelet‐derived growth factor receptor tyrosine kinase

Chan, Perry M.; Keller, Paul R.; Connors, Richard W.; Leopold, Wilbur R.; Miller, W. Todd

doi:10.1016/0014-5793(96)00898-8

Cited by 12 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peptide libraries containing randomized residues adjacent to the phosphorylatable tyrosine have been used to determine substrate specificities of various tyrosine kinases. 21,[54][55][56] For H-IR, these studies resulted in the identification of the E4YM4 sequence as an efficient peptide substrate. D-IRK exhibited strong catalytic activity against several peptide substrates, and like its human counterpart phosphorylated peptides with YxxM motifs.…”

Section: Discussionmentioning

confidence: 99%

Biochemical characterization of the Drosophila insulin receptor kinase and longevity‐associated mutants

Krishnan,

Ahmed,

Hubbard

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

Drosophila melanogaster (fruit fly) insulin receptor (D‐IR) is highly homologous to the human counterpart. Like the human pathway, D‐IR responds to numerous insulin‐like peptides to activate cellular signals that regulate growth, development, and lipid metabolism in fruit flies. Allelic mutations in the D‐IR kinase domain elevate life expectancy in fruit flies. We developed a robust heterologous expression system to express and purify wild‐type and longevity‐associated mutant D‐IR kinase domains to investigate enzyme kinetics and substrate specificities. D‐IR exhibits remarkable similarities to the human insulin receptor kinase domain but diverges in substrate preferences. We show that longevity‐associated mutations reduce D‐IR catalytic activity. Deletion of the unique kinase insert domain portion or mutations proximal to activating tyrosines do not influence kinase activity, suggesting their potential role in substrate recruitment and downstream signaling. Through biochemical investigations, this study enhances our comprehension of D‐IR's role in Drosophila physiology, complementing genetic studies and expanding our knowledge on the catalytic functions of this conserved signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Biochemical characterization of the Drosophila insulin receptor kinase and longevity‐associated mutants

Krishnan,

Ahmed,

Hubbard

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

show abstract

“…All peptides were purchased from Genemed Synthesis Inc. (San Antonio, TX, USA) and purified by semipreparative HPLC on a Vydac C18 column, lyophilized, and resuspended in Tris-HCl buffer pH 8.0, as previously described [29].…”

Section: Peptidesmentioning

confidence: 99%

Activity of the nonreceptor tyrosine kinase Ack1 is regulated by tyrosine phosphorylation of its Mig6 homology region

Kan

Miller

2022

FEBS Letters

View full text Add to dashboard Cite

Ack1 is a proto-oncogenic tyrosine kinase with homology to the tumour suppressor Mig6, an inhibitor of the epidermal growth factor receptor (EGFR). The residues critical for binding of Mig6 to EGFR are conserved within the Mig6 homology region (MHR) of Ack1. We tested whether intramolecular interactions between the Ack1 MHR and kinase domain (KD) are regulated by phosphorylation. We identified two Src phosphorylation sites within the MHR (Y859, Y860). Addition of Src-phosphorylated MHR to the Ack1 KD enhanced enzymatic activity. Co-expression of Src in cells led to increased Ack1 activity; mutation of Y859/Y860 blocked this increase. Collectively, the data suggest that phosphorylation of the Ack1 MHR regulates its kinase activity. Phosphorylation of Y859/Y860 occurs in cancers of the brain, breast, colon, and prostate, where genomic amplification or somatic mutations of Ack1 play a role in disease progression. Our findings suggest that MHR phosphorylation could contribute to Ack1 dysregulation in tumours.

show abstract

“…The details of these experiments are given in our June 1999 Progress Report. Neu phosphorylation of peptide library I was carried out using procedures we established previously for PDGF receptor phosphorylation (5). Briefly, Neu reactions with the library were carried out in the presence of [y -32 P]ATP.…”

Section: Task 2 Preparation Of Peptide Librariesmentioning

confidence: 99%

“…Substrate sequences for Neu identified in this study, along with kinetic parameters for phosphorylation. were carried out using the continuous spectrophotometric assay (5). Peptide 6 contains a control sequence.…”

Section: Task 2 Test Peptides As Inhibitors Of Neu In Vivomentioning

confidence: 99%

Peptide-Based Inhibitors of Neu Tyrosine Kinase

Miller¹

2000

View full text Add to dashboard Cite

Amino‐terminal sequence determinants for substrate recognition by platelet‐derived growth factor receptor tyrosine kinase

Cited by 12 publications

References 32 publications

Biochemical characterization of the Drosophila insulin receptor kinase and longevity‐associated mutants

Biochemical characterization of the Drosophila insulin receptor kinase and longevity‐associated mutants

Activity of the nonreceptor tyrosine kinase Ack1 is regulated by tyrosine phosphorylation of its Mig6 homology region

Peptide-Based Inhibitors of Neu Tyrosine Kinase

Contact Info

Product

Resources

About