Related Experiment Video

Updated: Aug 5, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

The RAF family: an expanding network of post-translational controls and protein-protein interactions

A Yuryev1, L P Wennogle

  • 1Novartis Pharmaceuticals Corporation, Summit, NJ 07901, USA. Lawrence.Wennogle@pharma.novartis.com

Cell Research
|July 21, 1998
PubMed

Insights

RAF protein kinases regulate cell proliferation via the Ras-MAPK pathway. Recent studies reveal isoform-specific protein interactions, suggesting distinct functions for RAF isoforms beyond Ras-mediated signaling.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Cancer research

Background:

  • The Ras-MAPK pathway is crucial for transmitting signals from growth factors to the nucleus, driving cell proliferation.
  • RAF kinases are key components, phosphorylating MEK, which then activates MAP-kinase.
  • RAF regulation involves complex signaling networks beyond Ras, including kinases and protein-protein interactions.

Purpose of the Study:

  • To explore the regulatory mechanisms of RAF protein kinases.
  • To investigate the potential for isoform-specific functions within the RAF family.
  • To understand the role of protein-protein interactions in RAF isoform regulation.

Main Methods:

  • Analysis of the Ras-MAP-kinase signal transduction pathway.
  • Investigating orthogonal signaling influences on RAF.
  • Identifying and characterizing isoform-specific protein interactions with RAF.

Main Results:

  • RAF kinases are central to the Ras-MAPK pathway controlling cell proliferation.
  • RAF regulation is influenced by various signaling inputs beyond Ras.
  • Three RAF isoforms exist with divergent regulatory domains.
  • Emerging evidence points to isoform-specific protein interactions.

Conclusions:

  • RAF isoforms may possess distinct functions, potentially mediated by specific protein interactions.
  • Understanding these isoform-specific interactions is key to delineating independent RAF functions.
  • This research opens avenues for targeted therapies by exploiting RAF isoform differences.

More Related Videos

Novel RNA-Binding Proteins Isolation by the RaPID Methodology11:19

Novel RNA-Binding Proteins Isolation by the RaPID Methodology

Published on: September 30, 2016

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Rab Cascades01:25

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
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,...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...