Cdc42 protein signal transduction
Definition
Target type: biologicalprocess
An intracellular signaling cassette in which a small monomeric GTPase of the Cdc42 subfamily relays a signal. [GOC:mah, PMID:18558478]
Cdc42 is a small GTPase protein that plays a critical role in regulating a wide range of cellular processes, including cell polarity, cytoskeletal organization, cell migration, and cell division. Cdc42 signal transduction is initiated by the binding of guanosine triphosphate (GTP) to the protein, which triggers a conformational change that activates Cdc42. This activation allows Cdc42 to interact with a variety of downstream effector proteins, leading to the initiation of signaling cascades that ultimately control cellular behavior.
The process of Cdc42 signal transduction can be broadly divided into the following steps:
1. **Activation of Cdc42:** The activation of Cdc42 is regulated by a family of guanine nucleotide exchange factors (GEFs), which promote the exchange of GDP for GTP. Activated Cdc42 can then interact with a variety of effector proteins.
2. **Interaction with effector proteins:** Activated Cdc42 interacts with a variety of effector proteins, including:
- **PAK (p21-activated kinase) family kinases:** PAK kinases are involved in a wide range of cellular processes, including cytoskeletal reorganization, cell migration, and gene expression.
- **WASp (Wiskott-Aldrich syndrome protein) family proteins:** WASp proteins are involved in the regulation of actin polymerization, which is essential for cell motility and cell division.
- **IQGAPs (IQ motif containing GTPase activating protein):** IQGAPs are scaffold proteins that link Cdc42 to other signaling pathways, including the Ras pathway.
3. **Downstream signaling:** The interaction of Cdc42 with its effector proteins triggers downstream signaling cascades that regulate cellular behavior. For example, activation of PAK kinases can lead to the phosphorylation of downstream targets, such as LIM kinases, which in turn regulate actin cytoskeleton dynamics.
4. **Inactivation of Cdc42:** The activity of Cdc42 is tightly regulated, and it is inactivated by GTPase-activating proteins (GAPs) which stimulate the hydrolysis of GTP to GDP. This ensures that Cdc42 signaling is transient and does not persist for extended periods.
The precise biological outcomes of Cdc42 signaling depend on the specific effector proteins that are activated, the cellular context, and other signaling inputs. Aberrant Cdc42 signaling has been implicated in a variety of diseases, including cancer and developmental disorders.
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Cell division control protein 42 homolog | A cell division control protein 42 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P60953] | Homo sapiens (human) |
Compounds (7)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| fasudil | fasudil : An isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia. fasudil: intracellular calcium antagonist; structure in first source | isoquinolines; N-sulfonyldiazepane | antihypertensive agent; calcium channel blocker; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; geroprotector; neuroprotective agent; nootropic agent; vasodilator agent |
| ketorolac | 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid : A member of the class of pyrrolizines that is 2,3-dihydro-1H-pyrrolizine which is substituted at positions 1 and 5 by carboxy and benzoyl groups, respectively. ketorolac : A racemate comprising equimolar amounts of (R)-(+)- and (S)-(-)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid. While only the (S)-(-) enantiomer is a COX1 and COX2 inhibitor, the (R)-(+) enantiomer exhibits potent analgesic activity. A non-steroidal anti-inflammatory drug, ketorolac is mainly used (generally as the tromethamine salt) for its potent analgesic properties in the short-term management of post-operative pain, and in eye drops to relieve the ocular itching associated with seasonal allergic conjunctivitis. It was withdrawn from the market in many countries in 1993 following association with haemorrhage and renal failure. Ketorolac: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed) | amino acid; aromatic ketone; monocarboxylic acid; pyrrolizines; racemate | analgesic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; non-steroidal anti-inflammatory drug |
| sanguinarine chloride | |||
| chelerythrine chloride | |||
| 2-[[benzamido(sulfanylidene)methyl]amino]-5,5-dimethyl-4,7-dihydrothieno[2,3-c]pyran-3-carboxylic acid | CID1067700: a pan-GTPase inhibitor; structure in first source | thienopyran | |
| y 27632, dihydrochloride, (4(r)-trans)-isomer | |||
| secramine a | secramine A: inhibits VSVG transport from the Golgi to the plasma membrane; also inhibits Cdc42-dependent cell functions; structure in first source |