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Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
Graded and Abrupt Responses
Some signaling systems generate...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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,...

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Coordinate expression and functional profiling identify an extracellular proteolytic signaling pathway.

Ami S Bhatt1, Alana Welm, Christopher J Farady

  • 1Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, CA 94158, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 29, 2007
PubMed
Summary

Researchers identified a protease-activated signaling pathway involving MT-SP1, MSP-1, and RON. This pathway regulates macrophage activation and may be involved in cancer progression.

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Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Protease-activated signaling pathways are crucial in cellular communication.
  • Dysregulation of signaling pathways, including MT-SP1 and RON, is linked to cancer progression and metastasis.

Purpose of the Study:

  • To identify novel substrates and characterize protease-activated signaling pathways.
  • To elucidate the role of MT-SP1 in the activation of MSP-1 and subsequent macrophage function.

Main Methods:

  • Integration of protease substrate profiling with microarray gene coexpression data from human tissues.
  • Biochemical assays to confirm enzyme activity in vitro and in cellular contexts.
  • Inhibition studies using HAI-1 and MT-SP1-specific antibodies.

Main Results:

  • Identified a signaling pathway comprising MT-SP1, MSP-1, and RON.
  • Demonstrated MT-SP1's role in cleaving and activating pro-MSP-1, leading to nitric oxide inhibition in macrophages.
  • Confirmed that MT-SP1, MSP-1, and RON are essential for peritoneal macrophage activation.

Conclusions:

  • MT-SP1 is sufficient for MSP-1 activation, forming a novel protease-activated signaling pathway.
  • This pathway, involving MT-SP1, MSP-1, and RON, is implicated in macrophage activation and potentially in human cancers.