Related Experiment Video

Updated: May 21, 2026

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes
10:05

In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes

Published on: August 13, 2012

Commentary: The carboxyl-terminal Crk SH3 domain: Regulatory strategies and new perspectives

Ganapathy Sriram1, Raymond B Birge

  • 1Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.

FEBS Letters
|June 20, 2012
PubMed

Insights

The Crk protein

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • The Crk family of proteins are crucial in signal transduction pathways.
  • Their role as viral oncogene counterparts has been known for over two decades.
  • Understanding Crk protein regulation is key to deciphering cellular signaling.

Purpose of the Study:

  • To investigate the novel regulatory mechanisms of the Crk protein.
  • To explore the function of the atypical carboxyl-terminal SH3 domain (SH3C) in Crk regulation.
  • To uncover new signaling strategies employed by adaptor proteins.

Main Methods:

  • Structural and biochemical studies were employed.
  • Analysis of tyrosine phosphorylation of the Crk SH3C domain.
  • Investigation of protein-protein interactions mediated by SH3C.

Main Results:

  • New insights into both negative and positive regulation of Crk were uncovered.
  • The carboxyl-terminal SH3 domain (SH3C) plays a key role in Crk regulation.
  • Tyrosine phosphorylation of SH3C by various kinases allows binding of SH2/PTB domain proteins.

Conclusions:

  • The Crk SH3C domain exhibits non-canonical signaling capabilities.
  • This atypical signaling provides novel regulatory strategies for adaptor proteins.
  • Findings advance the understanding of Crk-mediated signal transduction.

More Related Videos

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion09:23

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion

Published on: April 2, 2020

Combining Wet and Dry Lab Techniques to Guide the Crystallization of Large Coiled-coil Containing Proteins11:14

Combining Wet and Dry Lab Techniques to Guide the Crystallization of Large Coiled-coil Containing Proteins

Published on: January 6, 2017

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...