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Rabbit Anti-phospho-CRK (Tyr221)/FITC Conjugated antibody
background:
Crk p38 (CrkII) is an isoform of the protein Crk. CrkI and CrkII are produced from the same crk gene by alternative splicing. The two isoforms differ in their biological activities with CrkII having less transforming activity than CrkI.
Crk p38 is a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. It has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the SLCterminal SH3 domain functions as a negative regulator of transformation.
Crk is believed to be a regulator of invasive responses because increased levels of the protein have been observed in multiple human cancers. In vivo studies have demonstrated that decreased levels of Crk remarkably inhibits tumor formation and its invasive growth.
Function:
The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling.
Subunit:
Interacts with ABL1, C3G, SOS, MAP4K1, MAPK8 and DOCK3 via its first SH3 domain. Interacts (via SH2 domain) with BCAR1, CBL, CBLB, PXN, IRS4 and GAB1 upon stimulus-induced tyrosine phosphorylation. Interacts (via SH2 domain) with several tyrosine-phosphorylated growth factor receptors such as EGFR and INSR. Interacts with FLT1 (tyrosine-phosphorylated) (By similarity). Interacts with DOCK1 and DOCK4. Interacts with SHB. Interacts with PEAK1. Interacts with FASLG. Isoform Crk-II interacts with KIT. Interacts with EPHA3; upon activation of EPHA3 by the ligand EFNA5 and EPHA3 tyrosine kinase activity-dependent. Interacts with EPHA3 (phosphorylated); mediates EFNA5-EPHA3 signaling through RHOA GTPase activation. Interacts with FLT4 (tyrosine-phosphorylated). Isoform Crk-II (via SH2 domain) interacts with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and p130cas/BCAR1. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1.
Subcellular Location:
Cytoplasm. Cell membrane. Note=Translocated to the plasma membrane upon cell adhesion.
Post-translational modifications:
Phosphorylation of Crk-II (40 kDa) gives rise to a 42 kDa form. Isoform Crk-II is phosphorylated by KIT.
Phosphorylated on Tyr-221 upon cell adhesion. Results in the negative regulation of the association with SH2- and SH3-binding partners, possibly by the formation of an intramolecular interaction of phosphorylated Tyr-221 with the SH2 domain. This leads finally to the down-regulation of the Crk signaling pathway.
Proline isomerization at Pro-237 by PPIA acts as a switch between two conformations: an autoinhibitory conformation in the cis form, where the tandem SH3 domains interact intramolecularly, and an activated conformation in the trans form.
Similarity:
Belongs to the CRK family.
Contains 1 SH2 domain.
Contains 2 SH3 domains.
Database links:
Entrez Gene: 1398 Human
Entrez Gene: 12928 Mouse
Entrez Gene: 54245 Rat
Omim: 164762 Human
SwissProt: P46108 Human
SwissProt: Q96GA9 Human
SwissProt: Q96HJ0 Human
SwissProt: Q12810 Mouse
SwissProt: Q63768 Rat
Unigene: 638121 Human
Unigene: 280125 Mouse
Unigene: 96136 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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