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RAF is an acronym for Rapidly Accelerated Fibrosarcoma. [12] RAF kinases participate in the RAS-RAF-MEK-ERK signal transduction cascade, also referred to as the mitogen-activated protein kinase (MAPK) cascade. [11] Activation of RAF kinases requires interaction with RAS-GTPases. The three RAF kinase family members are: A-RAF; B-RAF; c-Raf
The RAF kinase phosphorylates and activates a MAPK/ERK Kinase (MEK1 or MEK2). The MEK phosphorylates and activates a mitogen-activated protein kinase (MAPK). RAF and MAPK/ERK are both serine/threonine-specific protein kinases. MEK is a serine/tyrosine/threonine kinase. In a technical sense, RAF, MEK, and MAPK are all mitogen-activated kinases ...
RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme [4] that in humans is encoded by the RAF1 gene. [ 5 ] [ 6 ] The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase (MAP3K) that functions downstream of the Ras subfamily of membrane associated GTPases. [ 7 ]
The MAP kinase-kinase, which activates ERK, was named "MAPK/ERK kinase" . [5] Receptor-linked tyrosine kinases, Ras, Raf, MEK, and MAPK could be fitted into a signaling cascade linking an extracellular signal to MAPK activation. [6] See: MAPK/ERK pathway. Transgenic gene knockout mice lacking MAPK1 have major defects in early development. [7]
Progestin and adipoQ receptor family member 3 (PAQR3), or Raf Kinase Trapping to Golgi apparatus (RKTG) is a protein that in humans is encoded by the PAQR3 gene. [5] It is a member of the progestin and adipoQ receptor (PAQR) family. [6] PAQR3 is predicted to have seven transmembrane helices and to be localized to the Golgi Apparatus.
The figure shows the interaction and cooperation of MEK, DUSP5 and DUSP6/MKP-3 within the cytoplasmic region and the nucleus. RAF activates MEK. Activated MEK phoshorylates ERK which can now be transported across the cell membrane by a transporter. Dephosphorylated ERK cannot leave the nucleus.
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of serine/threonine-specific protein kinases involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines.
Activation of Ras has the potential to initiate three signaling pathways downstream of Ras: Ras→Raf→MAP kinase pathway, PI3 kinase pathway, and Ral pathway. Each pathway leads to the activation of transcription factors which enter the nucleus to alter gene expression. [9] Diagram showing key components of a signal transduction pathway.