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Printable Handouts
Navigable Slide Index
- Introduction
- Tyrosine phosphorylation
- The tyrosine phosphatase superfamily (HCx5R)
- The classical PTP family (HCSxGxGRxG)
- Goals
- Shps: a brief historical review
- Shps: similarities and differences
- Shp structure, enzymology and regulation
- Primary structure of Shps
- Role of the SH2 domains
- PTP catalytic mechanism
- Substrate trapping mutants
- Shps are regulated by their SH2 domains
- Crystal structure of the N-terminal of Shp2 (1)
- PTP/N-SH2 interface (open book)
- Crystal structure of the N-terminal of Shp2 (2)
- Regulation of Shp2 activity
- Other regulatory mechanisms (1)
- Other regulatory mechanisms (2)
- Physiological functions of Shps
- Previous Shp2 mutant mice
- Shp2 "null" mice
- Shp1 deficiency causes the Motheaten phenotype
- Shp2: role in RTK signaling
- Shp2 regulation of Ras-ERK pathway (1)
- Shp2 regulation of Ras-ERK pathway (2)
- Shp2 regulation of Ras-ERK pathway (3)
- Regulation of other pathways by Shp2
- Shp1: role in RTK signaling
- Shps in disease
- Noonan syndrome (NS): common human disorder
- Shp2 mutations and leukemia
- Juvenile myelomonocytic leukemia (JMML)
- Shp2 mutations in NS and leukemia
- Most disease-associated mutants map to interface
- Activated mutants cause NS and leukemia
- Shp2 mutant enzymology: summary
- NS mutants: signaling effects
- RTK pathways potentially perturbed in NS
- Shp2 mutants and leukemia
- Variations on the theme of activated mutants (1)
- Variations on the theme of activated mutants (2)
- Not all Shp2 mutants act as activated mutants
- LEOPARD syndrome (LS): Shp2 mutations
- LS mutants map to residues involved in catalysis
- LS mutants: enzymology and signaling effects
- Shps: key questions and challenges
Topics Covered
- Introduction to the PTP superfamily
- Shps, history and overview
- Shp stucture: role of SH2 domains, PTP domains, C-tail
- catalytic mechanism
- Regulation by phosphotyrosyl peptides, phosphorylation, reactive oxygen species
- Overview of physiological functions
- Role in RTK signaling: regulation of Ras/Erk pathway; roles in other downstream cascades
- Shps in disease
- Key questions and challenges for the future
Links
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Talk Citation
Neel, B.G. (2007, October 1). SH2-containing PTPs (Shps) in RTK signaling and disease [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/WBML3891.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Benjamin G. Neel has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.